腹膜血管新生引起腹膜超滤衰竭的机制及其阻断干预实验
|
摘要
背景和目的
终末期肾脏病(end stage renal disease, ESRD)已成为21世纪全人类面临的主要公共健康问题之一。腹膜透析(peritoneal dialysis, PD)是终末期肾脏病有效的治疗方法,具有保护残余肾功能、花费相对血液透析低等优势。但由于腹膜透析的并发症,如腹膜炎、营养不良、腹膜超滤衰竭,尤其透龄4-5年的患者,腹膜超滤衰竭发生率高达36%,已经成为腹膜透析患者被迫退出腹透的主要原因之一,因此探讨并干预腹膜透析超滤衰竭的发生与发展非常重要。
目前认为超滤衰竭的发病机制主要有三方面的因素：1、腹膜血管表面积的不断增加：约50%到75%的超滤衰竭是由于腹膜血管新生导致腹膜血管表面积的不断增加,使得小分子溶质转运加快致腹腔渗透压递度迅速消失,使腹膜超滤功能丧失；2、因为水通道蛋白失功能；3、腹膜间质/淋巴系统吸收增加。
腹膜血管新生可能是超滤衰竭发生的主要机制,调节血管新生的诱导剂有血管内皮生长因子(vascular endothelial growth factor,VEGF)、成纤维细胞生长因子(fibroblast growth factor,)等其它可溶性因子；抑制剂包括血管新生抑制素、内皮细胞抑制素(endostain, ES)等。目前认为血管生成时受到诱导因子和抑制因子的双重调节,正常情况下处于平衡状态,一旦诱导剂占优势,则激活血管长出新生血管,反之则使血管硬化。长期行腹膜透析的病人在其腹膜透析液中发现一些血管诱导剂增加,如VEGF、bFGF等,而且目前公认为血管内皮生长因子在腹透失超滤的发病机制中,是促进血管新生的主要因子,在血管新生中居于主导地位,并发现它在腹膜毛细血管内皮细胞和腹膜间皮细胞(peritoneal mesothelial cells, PMc)有阳性表达,但这些导致血管新生的因子表达增加的具体机制目前仍不清楚。综上所述我们有必要探讨腹膜血管新生在腹透失超滤发生机制所起的作用并进行干预研究,以便为延缓腹透失超滤的发生提供理论根据和实验依据,从而为多环节防治腹膜透析超滤衰竭的发生发展提供有效的治疗手段。
因此本研究共分三部分：
第一部分腹膜血管新生引起腹膜超滤衰竭的动物实验研究
构建5/6肾切除尿毒症大鼠模型,进而构建尿毒症腹膜透析大鼠模型。检测大鼠腹膜组织VEGF、bFGF及ES基因和蛋白质水平的表达变化,以及检测腹膜组织毛细血管密度(MVD),探讨腹膜新生血管引起大鼠腹膜透析超滤衰竭的机制,为了下一步干预实验打好理论基础。
第二部分腹膜血管新生引起腹膜超滤衰竭的临床研究
留取正常对照者(取自非尿毒症的腹部择期手术患者,排除任何可累及腹膜的疾病)、尿毒症非透析患者(尿毒症患者首次腹透置管时)以及腹透超滤衰竭患者(尿毒症患者拔出腹透管时)的腹膜活检标本。检测血管内皮生长因子、碱性成纤维生长因子和内皮抑素基因和蛋白质水平的表达,检测腹膜组织毛细血管密度。为下一步干预腹膜透析超滤衰竭的研究奠定理论基础。
第三部分重组人内皮抑素(恩度)干预腹膜血管新生的动物实验研究
应用重组人内皮抑素(恩度),干预大鼠腹膜透析腹膜血管新生,从而起到抑制腹膜血管新生,干预腹膜透析超滤衰竭的作用,为下一步治疗临床腹膜透析患者超滤衰竭提供实验根据。
第一部分腹膜血管新生引起腹膜超滤衰竭的动物实验研究
一.资料与方法
SD雄性大鼠42只,体重180-200g。构建5/6肾切除尿毒症大鼠模型,进而构建尿毒症腹膜透析大鼠模型。实验设立正常组(n=8只),手术组三组：尿毒症组(n=8只)、1.5%腹膜透析组(n=8只)、4.25%腹膜透析组(n=8只)。对各透析组大鼠进行规律腹透,每日每只20ml腹透液从大鼠颈部腹透管注入,腹腔保留2h后放出液体,规律透析28天后,取各组大鼠新鲜腹膜组织分别做逆转录聚合酶链反应(RT-PCR)及组织免疫组化,检测VEGF、bFGF及ES基因和蛋白质水平的表达变化,以CD34染色检测腹膜组织毛细血管密度(MVD),并进行统计学比较和基因水平的相关性分析,选取a=0.05作为差异具有统计学意义的检验水准。
二.结果
1. VEGF、bFGF及ES在正常大鼠腹膜组织中呈阳性表达。
2.与正常组相比较,尿毒症组、1.5%腹膜透析组、4.25%腹膜透析组,VEGF、bFGF在基因及蛋白的表达水平均升高,差异具有统计学意义(p<0.05)。
3.正常组、尿毒症组、1.5%腹膜透析组及4.25%腹膜透析组大鼠腹膜组织中均有ES mRNA表达。其中正常组为0.47±0.05；尿毒症组为0.45±0.04；1.5%腹膜透析组为0.46±0.04；4.25%腹膜透析组为0.47±0.03；各组间表达差异无统计学意义(P>0.05)。
4.正常组大鼠腹膜组织中ES蛋白表达积分0分；尿毒症组大鼠腹膜组织中积分2分；1.5%腹膜透析组大鼠腹膜组织中积分4分；4.25%腹膜透析组大鼠腹膜组织中呈高表达,积分9分。
5.与正常组相比较,尿毒症组、1.5%腹膜透析组、4.25%腹膜透析组大鼠腹膜组织中MVD的表达均增高,组间差异均有统计学意义(p<0.05)。
第二部分腹膜血管新生引起腹膜超滤衰竭的临床研究
一.资料与方法
留取正常对照者、尿毒症非透析患者以及腹透超滤衰竭患者的腹膜活检标本。将所留取的腹膜标本分别行逆转录聚合酶链反应(RT-PCR)和组织免疫组化染色,检测血管内皮生长因子、碱性成纤维生长因子和内皮抑素基因和蛋白质水平的表达。行CD34染色,计数腹膜组织毛细血管密度。
二.结果
1. VEGF、bFGF及ES的mRNA在各组人腹膜组织均有表达。与正常相比较,尿毒症非透析组、PD组腹膜组织VEGF、bFGF mRNA表达上调,差异具有统计学意义(P<0.05)；与尿毒症非透析组相比较,PD组腹膜组织VEGF、bFGF mRNA表达上调,差异具有统计学意义(P<0.05)。ES mRNA各组表达无差异。
2.各组腹膜组织均表达VEGF、bFGF及ES。与正常相比较,尿毒症非透析组、PD组腹膜组织VEGF、bFGF、ES蛋白表达上调,差异具有统计学意义(P<0.05)；与尿毒症非透析组相比较,PD组腹膜组织VEGF、bFGF、ES蛋白表达上调,差异具有统计学意义(P<0.05)。
3.MVD计数结果在正常组可见新生毛细血管较少或无,与正常组相比较,尿毒症非透析组、腹膜透析超滤衰竭组人腹膜组织MVD计数增加(P<0.05),差异具有统计学意义。
第三部分重组人内皮抑素(恩度)干预腹膜血管新生的动物
实验研究
一.资料与方法
清洁级雄性SD大鼠43只,体质量为180-200g。构建5/6肾切除尿毒症大鼠模型,进一步构建尿毒症腹膜透析大鼠模型。实验分为A：对照组(正常组：n=8只),B：尿毒症非透析组(5/6肾切除组：n=8只)、C：尿毒症腹膜透析组(生理盐水对照组：n=8只)、D1：重组人内皮抑素治疗1组(10mg/kg治疗组：n=8只),D2：重组人内皮抑素治疗2组(40mg/kg治疗组：n=8只)。对C、D1、D2组大鼠进行规律腹透,每日4.25%的腹透液从大鼠颈部腹透管注入,腹腔保留2h后放出液体,规律透析28天。D1、D2组(重组人内皮抑素治疗1、2组)在规律腹透期间,隔天皮下注射重组人内皮抑素,连续给药14次,直至腹透第28天结束,留取各组大鼠新鲜腹膜组织,采用免疫组织化学及逆转录聚合酶链反应(RT-PCR)的方法检测腹膜组织VEGF基因及蛋白水平的表达,用CD34染色观察各组大鼠腹膜血管数并计算腹膜组织毛细血管密度(Microvessel Density, MVD),所得结果进行统计学分析,选取α=0.05作为差异具有统计学意义的检验水准。
二.结果
1.与正常组相比较,尿毒症组、尿毒症腹膜透析组,VEGF基因及蛋白水平的表达均升高(p<0.05),差异具有统计学意义。与尿毒症腹膜透析组相比较,重组人内皮抑素治疗1组、重组人内皮抑素治疗2组,VEGF基因及蛋白水平的表达均降低(p<0.05),差异具有统计学意义。与重组人内皮抑素治疗1组相比较,重组人内皮抑素治疗2组,VEGF-A基因及蛋白水平的表达均降低(p<0.05),差异具有统计学意义。
2.与正常组相比较,尿毒症组、尿毒症腹膜透析组,MVD的值均增加(p<0.05),差异具有统计学意义。与尿毒症腹膜透析组相比较,重组人内皮抑素治疗1组、重组人内皮抑素治疗2组,MVD的值均降低(p<0.05),差异具有统计学意义。与重组人内皮抑素治疗1组相比较,重组人内皮抑素治疗2组,MVD的值降低(p<0.05),差异具有统计学意义。
3. VEGF基因水平的表达与MVD值呈现正相关,VEGF和尿毒症长期腹透时腹膜血管新生相关。
结论
1.大鼠和人的腹膜组织均表达VEGF、bFGF及ES,体内尿毒症环境和非生理性腹透液的刺激可以上调腹膜组织VEGF、bFGF基因和蛋白的表达。
2.尿毒症腹膜透析大鼠和人腹膜组织VEGF、bFGF基因及蛋白水平表达升高,可能在长期透析所致腹膜组织新生毛细血管形成过程中发挥一定的促血管新生作用,是腹透失超滤发生的重要因素之一。
3.体内尿毒症毒素和非生理性腹透液刺激可使大鼠和人的腹膜组织ES蛋白表达升高,在长期透析所致腹膜组织毛细血管生成增多中可能发挥一定的抑制血管生成作用。
4.重组人内皮抑素(恩度)能抑制尿毒症腹膜透析大鼠腹膜新生血管的形成,并且其抑制作用的强弱与药物的剂量有关。
5.重组人内皮抑素(恩度)可能是通过下调尿毒症腹膜透析大鼠腹膜组织中VEGF的表达而发挥抑制腹膜新生血管形成的作用。
Backgroud and Objective
End-stage renal disease (ESRD) has become one of the major public health problems which mankind must face up in the 21st century. Peritoneal dialysis (PD) is an effective way to treat end-stage renal disease. Compared with hemodialysis, PD has its own advantages, such as protecting residual renal function and lower cost. However, some complications often occur during peritoneal dialysis procedure, for example infections, malnutrition, ultrafiltration failure and so on. In particular, the rate of ultrafiltration failure was as high as 36% in these patients who have maitained peritoneal dialysis for 4-5 years. Ultrafiltration failure has become the main reason for peritoneal dialysis patients to withdraw from peritoneal dialysis. So it is greatly important to explore the reason of ultrafiltration failure and furthermore to intervent the occurrence of ultrafiltration failure of peritoneal dialysis.
The pathogenesis of ultrafiltration failure was currently considered to relate with three main factors. The first was the increased peritoneal vascular surface area:about 50% to 75% ultrafiltration failure was due to peritoneal angiogenesis that lead to the increased peritoneal vascular surface area, which would make the transport of small solutes speeded up and then induced abdominal osmotic pressure gradient rapidly disappearing, then the peritoneal ultrafiltration capacity lost.The second was the loss of function of aquqporins(AQPs) and the last was the increasing of peritoneal interstitial/lymph fluid reabsorbing rate.
Peritoneal neoangiogenesis was the main mechanism that dued to ultrafiltration failure. Regulating angiogenesis inducers included vascular endothelial growth factor (VEGF), fibroblast growth factor (aFGF and bFGF) and other soluble factors. Inhibitors included angiogenesis inhibin, Endostatin (ES) and so on. At present angiogenesis was regulated by inducing agents and inhibitors. Under normal circumstances they were in equilibrium, once the inducer was dominant, it would activate the blood vessels grow and shape the new blood vessels. Otherwise angiosclerosis would occur. A number of angiogenesis inducers increased in the peritoneal dialysis effluents of a long time peritoneal dialysis patients, such as VEGF, bFGF etc. Currently VEGF was recognized as the key factor in the pathogenesis of ultrafiltration failure and the promotion of angiogenesis. VEGF was in the dominant position during neoangiogenesis. The positive expression of VEGF was found in the peritoneal microvascular endothelial cells and peritoneal mesothelial cells (PMc), which was a hot topic in the field of international medical research. But the specific mechanism of angiogenesis factors was still not clear. In conclusion, it was necessary to study the role and the mechanism of peritoneal angiogenesis in peritoneal dialysis patients and to explore the ways to delay the occurrence of peritoneal dialysis ultrafiltration failure and provide a theoretical basis and experimental evidence. So it would provide an effective treatment for multiple control the occurrence of peritoneal dialysis ultrafiltration failure.
Therefore, the study was further divided into three parts.
Part I:Build 5/6 nephrectomy uremic rat model and then build uremic peritoneal dialysis rats. Detect the gene and protein expression of VEGF, bFGF and the ES, as well as detecting the microvessel desity of peritoneal tissue. Explore the mechanism of peritoneal angiogenesis. Set up the theoretical foundation for the intervention study.
Part II:Select peritoneal biopsies which were obtained from normal subjects, uremic predialysis patients and PD patients. And then the gene and protein expressions of VEGF、bFGF and ES were detected by human's peritoneum. Microvessel Density (MVD) was counted in each group. Set up a theoretical foundation for the further intervention study.
PartⅢ:Use recombinant human endostatin (Endostar) to inhibit peritoneal neoangiogenesis of urimic peritoneal dialysis rats. The aim is to provide clinical experimental basis for treating the ultrafiltration failure of peritoneal dialysis.
PartⅠAnimal experimentent Study of Neoangiogensis in Peritoneal Dialysis Ultrafiltration failure
Materials and Methods
The study was done in male SD rats of clean grade weighing 180-200g.We randomly selected 8 rats as normal group and established the uremia rats model of 5/6 nephrectomy and then from these uremia rats, we randomly established the peritoneal dialysis (PD) rats model. At last, there were 4 groups in this study:normal rats (n=8), uremia rats (n=8), dialysized rats exposed to PD 1.5% solution (n=8) and 4.25%(n=8) respectively. The catheters implanted in dialysis rats were tunneled subcutaneously to the neck and solutions 20ml per rat were kept in the abdominal cavity for 2 hours per day without anesthesia. After regularly peritoneal dialysis for 28 days, tissue immunohistochemistry methods and reverse transcript polymerase chain reaction (RT-PCR) were applied to detect the mRNA and protein expressions of VEGF、bFGF and ES in rats'peritoneal tissues of each group. Statistical analysis was performed to compare expressions and co relationship in each group. Significance was defined as a=0.05.
Results
1. VEGF、bFGF and ES were positively expressed in peritoneal tissues of normal rat.
2. Compared with normal group, the protein expression of VEGF、bFGF and ES were up-regulated in uremia rats and dialysized rats.
3. Compared with normal group, the mRNA expression of VEGF and bFGF were up-regulated in uremia rats and dialysized rats (p<0.05), but there was no significant difference (p>0.05).
4. In uremia rats (r=0.990, P=0.000),1.5% dialysized rats (r=0.925, P=0.000), 4.25% dialysized rats (r=0.968, P=0.000), there was a positive correlation between VEGF and bFGF in mRNA level.
5. MVD was up-regulated in uremia rats and dialysized rats compared with normal group (P<0.05).
PartⅡClinical research of the Mechanism of Neoangiogensis in
Peritoneal dialysis Ultrafiltration failure
Materials and Methods
Peritoneal biopsies were obtained from normal controls (from non-uremic patients with abdominal surgery, excluding any abdominal membrane disease), uremic predialysis patients at catheter insertion and PD patients at the time of catheter remove, reinsertion or renal transplantation. RT-PCR techniques and Immunohistochemical staining were used to investigate VEGF, bFGF and ES expression in peritoneal tissue. Microvessel density (MVD) of peritoneal tissue was assessed using immunohistochemistry with CD34 monoclonal antibody.
Results
1. The mRNA expression of VEGF and bFGF were found in all peritoneal samples in each group. Base on normal group, the mRNA expression of VEGF、bFGF in uremic predialysis and PD group were significantly up-regulated (P<0.05) Compared with uremic predialysis group, the mRNA expression of VEGF, bFGF in PD group were significantly up-regulated (P<0.05). The mRNA expression of ES was no significantly difference in each group.
2. The protein expression of VEGF and bFGF were found in all peritoneal samples in each group. Compared with normal group, the protein expression of VEGF、 bFGF and ES in uremic predialysis and PD group were significantly up-regulated (P<0.05). Compared with uremic predialysis group, the protein expression of VEGF, bFGF and ES in PD group were significantly up-regulated (P<0.05)
3. The new micro vascular vessels in normal group shows little or none. MVD was up-regulated in uremic predialysis and PD group compared with normal group (P<0.05).
PartⅢIntervention Study of Preventing the occurrence of Peritoneal Dialysis Ultrafiltration Failure
Materials and Methods
43 male SD rats of clean grade weighing 180-200g were used in the study. The uremia rats model was established by 5/6 nephrectomy and then from these uremia rats, we randomly established the peritoneal dialysis (PD) rats model. At last, there were 5 groups in this study:A:normal group (control group:n=8), B:uremia group (5/6 nephrectomy group:n=8), C:uremia peritoneal dialysis group (4.25% dialysized group:n=8), D1:the first treatment group with Endostar (10mg/kg treatment group: n=8), D2:the second treatment group with Endostar (40mg/kg treatment group:n=8). The rats from C, D1, D2 groups were given regular peritoneal dialysis. The catheters implanted in dialysis rats were tunneled subcutaneously to the neck and exchanged PD solutions per rat were kept in the abdominal cavity for 2 hours per day without anesthesia. The rats from D1, D2 groups accepted subcutaneous injection of Endostar during peritoneal dialysis period every other days, total administration 14 times. After regularly peritoneal dialysis for 28 days, tissue immunohistochemistry methods and reverse transcript polymerase chain reaction (RT-PCR) were applied to detect the mRNA and protein expressions of VEGF and in rats'peritoneal tissues of each group. Microvessel density (MVD) of peritoneal tissue was assessed using immunohistochemistry with CD34 monoclonal antibody. Statistical analysis was performed to compare with their expressions and co relationship in each group. Significance was defined as a=0.05.
Results
1. Base on normal group, the mRNA and protein expression of VEGF were significantly up-regulated in uremia group and uremia peritoneal dialysis group (P<0.05). Compared with uremia peritoneal dialysis group, the mRNA and protein expression of VEGF were significantly down-regulated in the first and second treatment groups with Endostar (P<0.05). Compared with the first treatment group with Endostar, the mRNA and protein expression of VEGF were significantly down-regulated in the second treatment group with Endostar (P<0.05)
2. Base on the normal group, MVD was up-regulated in uremia group and uremia peritoneal dialysis group (P<0.05). Compared with uremia peritoneal dialysis group, MVD was significantly down-regulated in the first and second treatment groups with Endostar (P<0.05). Compared with the first treatment group with Endostar, MVD was significantly down-regulated in the second treatment group with Endostar (P<0.05)
3. There was a positive correlation between VEGF and MVD in protein level (r=0.987, P=0.000)
Conclusions
1. The expression of VEGF、bFGF and ES was positive in peritoneal tissues both normal rats and human; the expression of VEGF、bFGF and ES was up-regulated by uremia circumstance and non-physiological compatibility peritoneal dialysis liquid.
2. The upregulation of VEGF and bFGF in peritoneal dialysis rat and patient peritoneum might participate in the increasement of the peritoneum neoangiogensis and then cause the incidence of ultrafiltration.
3. The protein level expression of ES was up-regulated by uremia circumstance and non-physiological compatibility peritoneal dialysis liquid. ES might play an important role in inhibitting peritoneum neoangiogensis
4. Recombinant human endostatin (Endostar) can effectively inhibit rat peritoneum neoangiogensis inducing by peritoneal dialysis, and the role of inhibit strength is related with the dose of the drug.
5. Recombinant human endostatin (Endostar) can inhibit rat peritoneum neoangiogensis by down-regulating the expression of VEGF in peritoneum.
终末期肾脏病(end stage renal disease, ESRD)已成为21世纪全人类面临的主要公共健康问题之一。腹膜透析(peritoneal dialysis, PD)是终末期肾脏病有效的治疗方法,具有保护残余肾功能、花费相对血液透析低等优势。但由于腹膜透析的并发症,如腹膜炎、营养不良、腹膜超滤衰竭,尤其透龄4-5年的患者,腹膜超滤衰竭发生率高达36%,已经成为腹膜透析患者被迫退出腹透的主要原因之一,因此探讨并干预腹膜透析超滤衰竭的发生与发展非常重要。
目前认为超滤衰竭的发病机制主要有三方面的因素：1、腹膜血管表面积的不断增加：约50%到75%的超滤衰竭是由于腹膜血管新生导致腹膜血管表面积的不断增加,使得小分子溶质转运加快致腹腔渗透压递度迅速消失,使腹膜超滤功能丧失；2、因为水通道蛋白失功能；3、腹膜间质/淋巴系统吸收增加。
腹膜血管新生可能是超滤衰竭发生的主要机制,调节血管新生的诱导剂有血管内皮生长因子(vascular endothelial growth factor,VEGF)、成纤维细胞生长因子(fibroblast growth factor,)等其它可溶性因子；抑制剂包括血管新生抑制素、内皮细胞抑制素(endostain, ES)等。目前认为血管生成时受到诱导因子和抑制因子的双重调节,正常情况下处于平衡状态,一旦诱导剂占优势,则激活血管长出新生血管,反之则使血管硬化。长期行腹膜透析的病人在其腹膜透析液中发现一些血管诱导剂增加,如VEGF、bFGF等,而且目前公认为血管内皮生长因子在腹透失超滤的发病机制中,是促进血管新生的主要因子,在血管新生中居于主导地位,并发现它在腹膜毛细血管内皮细胞和腹膜间皮细胞(peritoneal mesothelial cells, PMc)有阳性表达,但这些导致血管新生的因子表达增加的具体机制目前仍不清楚。综上所述我们有必要探讨腹膜血管新生在腹透失超滤发生机制所起的作用并进行干预研究,以便为延缓腹透失超滤的发生提供理论根据和实验依据,从而为多环节防治腹膜透析超滤衰竭的发生发展提供有效的治疗手段。
因此本研究共分三部分：
第一部分腹膜血管新生引起腹膜超滤衰竭的动物实验研究
构建5/6肾切除尿毒症大鼠模型,进而构建尿毒症腹膜透析大鼠模型。检测大鼠腹膜组织VEGF、bFGF及ES基因和蛋白质水平的表达变化,以及检测腹膜组织毛细血管密度(MVD),探讨腹膜新生血管引起大鼠腹膜透析超滤衰竭的机制,为了下一步干预实验打好理论基础。
第二部分腹膜血管新生引起腹膜超滤衰竭的临床研究
留取正常对照者(取自非尿毒症的腹部择期手术患者,排除任何可累及腹膜的疾病)、尿毒症非透析患者(尿毒症患者首次腹透置管时)以及腹透超滤衰竭患者(尿毒症患者拔出腹透管时)的腹膜活检标本。检测血管内皮生长因子、碱性成纤维生长因子和内皮抑素基因和蛋白质水平的表达,检测腹膜组织毛细血管密度。为下一步干预腹膜透析超滤衰竭的研究奠定理论基础。
第三部分重组人内皮抑素(恩度)干预腹膜血管新生的动物实验研究
应用重组人内皮抑素(恩度),干预大鼠腹膜透析腹膜血管新生,从而起到抑制腹膜血管新生,干预腹膜透析超滤衰竭的作用,为下一步治疗临床腹膜透析患者超滤衰竭提供实验根据。
第一部分腹膜血管新生引起腹膜超滤衰竭的动物实验研究
一.资料与方法
SD雄性大鼠42只,体重180-200g。构建5/6肾切除尿毒症大鼠模型,进而构建尿毒症腹膜透析大鼠模型。实验设立正常组(n=8只),手术组三组：尿毒症组(n=8只)、1.5%腹膜透析组(n=8只)、4.25%腹膜透析组(n=8只)。对各透析组大鼠进行规律腹透,每日每只20ml腹透液从大鼠颈部腹透管注入,腹腔保留2h后放出液体,规律透析28天后,取各组大鼠新鲜腹膜组织分别做逆转录聚合酶链反应(RT-PCR)及组织免疫组化,检测VEGF、bFGF及ES基因和蛋白质水平的表达变化,以CD34染色检测腹膜组织毛细血管密度(MVD),并进行统计学比较和基因水平的相关性分析,选取a=0.05作为差异具有统计学意义的检验水准。
二.结果
1. VEGF、bFGF及ES在正常大鼠腹膜组织中呈阳性表达。
2.与正常组相比较,尿毒症组、1.5%腹膜透析组、4.25%腹膜透析组,VEGF、bFGF在基因及蛋白的表达水平均升高,差异具有统计学意义(p<0.05)。
3.正常组、尿毒症组、1.5%腹膜透析组及4.25%腹膜透析组大鼠腹膜组织中均有ES mRNA表达。其中正常组为0.47±0.05；尿毒症组为0.45±0.04；1.5%腹膜透析组为0.46±0.04；4.25%腹膜透析组为0.47±0.03；各组间表达差异无统计学意义(P>0.05)。
4.正常组大鼠腹膜组织中ES蛋白表达积分0分；尿毒症组大鼠腹膜组织中积分2分；1.5%腹膜透析组大鼠腹膜组织中积分4分；4.25%腹膜透析组大鼠腹膜组织中呈高表达,积分9分。
5.与正常组相比较,尿毒症组、1.5%腹膜透析组、4.25%腹膜透析组大鼠腹膜组织中MVD的表达均增高,组间差异均有统计学意义(p<0.05)。
第二部分腹膜血管新生引起腹膜超滤衰竭的临床研究
一.资料与方法
留取正常对照者、尿毒症非透析患者以及腹透超滤衰竭患者的腹膜活检标本。将所留取的腹膜标本分别行逆转录聚合酶链反应(RT-PCR)和组织免疫组化染色,检测血管内皮生长因子、碱性成纤维生长因子和内皮抑素基因和蛋白质水平的表达。行CD34染色,计数腹膜组织毛细血管密度。
二.结果
1. VEGF、bFGF及ES的mRNA在各组人腹膜组织均有表达。与正常相比较,尿毒症非透析组、PD组腹膜组织VEGF、bFGF mRNA表达上调,差异具有统计学意义(P<0.05)；与尿毒症非透析组相比较,PD组腹膜组织VEGF、bFGF mRNA表达上调,差异具有统计学意义(P<0.05)。ES mRNA各组表达无差异。
2.各组腹膜组织均表达VEGF、bFGF及ES。与正常相比较,尿毒症非透析组、PD组腹膜组织VEGF、bFGF、ES蛋白表达上调,差异具有统计学意义(P<0.05)；与尿毒症非透析组相比较,PD组腹膜组织VEGF、bFGF、ES蛋白表达上调,差异具有统计学意义(P<0.05)。
3.MVD计数结果在正常组可见新生毛细血管较少或无,与正常组相比较,尿毒症非透析组、腹膜透析超滤衰竭组人腹膜组织MVD计数增加(P<0.05),差异具有统计学意义。
第三部分重组人内皮抑素(恩度)干预腹膜血管新生的动物
实验研究
一.资料与方法
清洁级雄性SD大鼠43只,体质量为180-200g。构建5/6肾切除尿毒症大鼠模型,进一步构建尿毒症腹膜透析大鼠模型。实验分为A：对照组(正常组：n=8只),B：尿毒症非透析组(5/6肾切除组：n=8只)、C：尿毒症腹膜透析组(生理盐水对照组：n=8只)、D1：重组人内皮抑素治疗1组(10mg/kg治疗组：n=8只),D2：重组人内皮抑素治疗2组(40mg/kg治疗组：n=8只)。对C、D1、D2组大鼠进行规律腹透,每日4.25%的腹透液从大鼠颈部腹透管注入,腹腔保留2h后放出液体,规律透析28天。D1、D2组(重组人内皮抑素治疗1、2组)在规律腹透期间,隔天皮下注射重组人内皮抑素,连续给药14次,直至腹透第28天结束,留取各组大鼠新鲜腹膜组织,采用免疫组织化学及逆转录聚合酶链反应(RT-PCR)的方法检测腹膜组织VEGF基因及蛋白水平的表达,用CD34染色观察各组大鼠腹膜血管数并计算腹膜组织毛细血管密度(Microvessel Density, MVD),所得结果进行统计学分析,选取α=0.05作为差异具有统计学意义的检验水准。
二.结果
1.与正常组相比较,尿毒症组、尿毒症腹膜透析组,VEGF基因及蛋白水平的表达均升高(p<0.05),差异具有统计学意义。与尿毒症腹膜透析组相比较,重组人内皮抑素治疗1组、重组人内皮抑素治疗2组,VEGF基因及蛋白水平的表达均降低(p<0.05),差异具有统计学意义。与重组人内皮抑素治疗1组相比较,重组人内皮抑素治疗2组,VEGF-A基因及蛋白水平的表达均降低(p<0.05),差异具有统计学意义。
2.与正常组相比较,尿毒症组、尿毒症腹膜透析组,MVD的值均增加(p<0.05),差异具有统计学意义。与尿毒症腹膜透析组相比较,重组人内皮抑素治疗1组、重组人内皮抑素治疗2组,MVD的值均降低(p<0.05),差异具有统计学意义。与重组人内皮抑素治疗1组相比较,重组人内皮抑素治疗2组,MVD的值降低(p<0.05),差异具有统计学意义。
3. VEGF基因水平的表达与MVD值呈现正相关,VEGF和尿毒症长期腹透时腹膜血管新生相关。
结论
1.大鼠和人的腹膜组织均表达VEGF、bFGF及ES,体内尿毒症环境和非生理性腹透液的刺激可以上调腹膜组织VEGF、bFGF基因和蛋白的表达。
2.尿毒症腹膜透析大鼠和人腹膜组织VEGF、bFGF基因及蛋白水平表达升高,可能在长期透析所致腹膜组织新生毛细血管形成过程中发挥一定的促血管新生作用,是腹透失超滤发生的重要因素之一。
3.体内尿毒症毒素和非生理性腹透液刺激可使大鼠和人的腹膜组织ES蛋白表达升高,在长期透析所致腹膜组织毛细血管生成增多中可能发挥一定的抑制血管生成作用。
4.重组人内皮抑素(恩度)能抑制尿毒症腹膜透析大鼠腹膜新生血管的形成,并且其抑制作用的强弱与药物的剂量有关。
5.重组人内皮抑素(恩度)可能是通过下调尿毒症腹膜透析大鼠腹膜组织中VEGF的表达而发挥抑制腹膜新生血管形成的作用。
Backgroud and Objective
End-stage renal disease (ESRD) has become one of the major public health problems which mankind must face up in the 21st century. Peritoneal dialysis (PD) is an effective way to treat end-stage renal disease. Compared with hemodialysis, PD has its own advantages, such as protecting residual renal function and lower cost. However, some complications often occur during peritoneal dialysis procedure, for example infections, malnutrition, ultrafiltration failure and so on. In particular, the rate of ultrafiltration failure was as high as 36% in these patients who have maitained peritoneal dialysis for 4-5 years. Ultrafiltration failure has become the main reason for peritoneal dialysis patients to withdraw from peritoneal dialysis. So it is greatly important to explore the reason of ultrafiltration failure and furthermore to intervent the occurrence of ultrafiltration failure of peritoneal dialysis.
The pathogenesis of ultrafiltration failure was currently considered to relate with three main factors. The first was the increased peritoneal vascular surface area:about 50% to 75% ultrafiltration failure was due to peritoneal angiogenesis that lead to the increased peritoneal vascular surface area, which would make the transport of small solutes speeded up and then induced abdominal osmotic pressure gradient rapidly disappearing, then the peritoneal ultrafiltration capacity lost.The second was the loss of function of aquqporins(AQPs) and the last was the increasing of peritoneal interstitial/lymph fluid reabsorbing rate.
Peritoneal neoangiogenesis was the main mechanism that dued to ultrafiltration failure. Regulating angiogenesis inducers included vascular endothelial growth factor (VEGF), fibroblast growth factor (aFGF and bFGF) and other soluble factors. Inhibitors included angiogenesis inhibin, Endostatin (ES) and so on. At present angiogenesis was regulated by inducing agents and inhibitors. Under normal circumstances they were in equilibrium, once the inducer was dominant, it would activate the blood vessels grow and shape the new blood vessels. Otherwise angiosclerosis would occur. A number of angiogenesis inducers increased in the peritoneal dialysis effluents of a long time peritoneal dialysis patients, such as VEGF, bFGF etc. Currently VEGF was recognized as the key factor in the pathogenesis of ultrafiltration failure and the promotion of angiogenesis. VEGF was in the dominant position during neoangiogenesis. The positive expression of VEGF was found in the peritoneal microvascular endothelial cells and peritoneal mesothelial cells (PMc), which was a hot topic in the field of international medical research. But the specific mechanism of angiogenesis factors was still not clear. In conclusion, it was necessary to study the role and the mechanism of peritoneal angiogenesis in peritoneal dialysis patients and to explore the ways to delay the occurrence of peritoneal dialysis ultrafiltration failure and provide a theoretical basis and experimental evidence. So it would provide an effective treatment for multiple control the occurrence of peritoneal dialysis ultrafiltration failure.
Therefore, the study was further divided into three parts.
Part I:Build 5/6 nephrectomy uremic rat model and then build uremic peritoneal dialysis rats. Detect the gene and protein expression of VEGF, bFGF and the ES, as well as detecting the microvessel desity of peritoneal tissue. Explore the mechanism of peritoneal angiogenesis. Set up the theoretical foundation for the intervention study.
Part II:Select peritoneal biopsies which were obtained from normal subjects, uremic predialysis patients and PD patients. And then the gene and protein expressions of VEGF、bFGF and ES were detected by human's peritoneum. Microvessel Density (MVD) was counted in each group. Set up a theoretical foundation for the further intervention study.
PartⅢ:Use recombinant human endostatin (Endostar) to inhibit peritoneal neoangiogenesis of urimic peritoneal dialysis rats. The aim is to provide clinical experimental basis for treating the ultrafiltration failure of peritoneal dialysis.
PartⅠAnimal experimentent Study of Neoangiogensis in Peritoneal Dialysis Ultrafiltration failure
Materials and Methods
The study was done in male SD rats of clean grade weighing 180-200g.We randomly selected 8 rats as normal group and established the uremia rats model of 5/6 nephrectomy and then from these uremia rats, we randomly established the peritoneal dialysis (PD) rats model. At last, there were 4 groups in this study:normal rats (n=8), uremia rats (n=8), dialysized rats exposed to PD 1.5% solution (n=8) and 4.25%(n=8) respectively. The catheters implanted in dialysis rats were tunneled subcutaneously to the neck and solutions 20ml per rat were kept in the abdominal cavity for 2 hours per day without anesthesia. After regularly peritoneal dialysis for 28 days, tissue immunohistochemistry methods and reverse transcript polymerase chain reaction (RT-PCR) were applied to detect the mRNA and protein expressions of VEGF、bFGF and ES in rats'peritoneal tissues of each group. Statistical analysis was performed to compare expressions and co relationship in each group. Significance was defined as a=0.05.
Results
1. VEGF、bFGF and ES were positively expressed in peritoneal tissues of normal rat.
2. Compared with normal group, the protein expression of VEGF、bFGF and ES were up-regulated in uremia rats and dialysized rats.
3. Compared with normal group, the mRNA expression of VEGF and bFGF were up-regulated in uremia rats and dialysized rats (p<0.05), but there was no significant difference (p>0.05).
4. In uremia rats (r=0.990, P=0.000),1.5% dialysized rats (r=0.925, P=0.000), 4.25% dialysized rats (r=0.968, P=0.000), there was a positive correlation between VEGF and bFGF in mRNA level.
5. MVD was up-regulated in uremia rats and dialysized rats compared with normal group (P<0.05).
PartⅡClinical research of the Mechanism of Neoangiogensis in
Peritoneal dialysis Ultrafiltration failure
Materials and Methods
Peritoneal biopsies were obtained from normal controls (from non-uremic patients with abdominal surgery, excluding any abdominal membrane disease), uremic predialysis patients at catheter insertion and PD patients at the time of catheter remove, reinsertion or renal transplantation. RT-PCR techniques and Immunohistochemical staining were used to investigate VEGF, bFGF and ES expression in peritoneal tissue. Microvessel density (MVD) of peritoneal tissue was assessed using immunohistochemistry with CD34 monoclonal antibody.
Results
1. The mRNA expression of VEGF and bFGF were found in all peritoneal samples in each group. Base on normal group, the mRNA expression of VEGF、bFGF in uremic predialysis and PD group were significantly up-regulated (P<0.05) Compared with uremic predialysis group, the mRNA expression of VEGF, bFGF in PD group were significantly up-regulated (P<0.05). The mRNA expression of ES was no significantly difference in each group.
2. The protein expression of VEGF and bFGF were found in all peritoneal samples in each group. Compared with normal group, the protein expression of VEGF、 bFGF and ES in uremic predialysis and PD group were significantly up-regulated (P<0.05). Compared with uremic predialysis group, the protein expression of VEGF, bFGF and ES in PD group were significantly up-regulated (P<0.05)
3. The new micro vascular vessels in normal group shows little or none. MVD was up-regulated in uremic predialysis and PD group compared with normal group (P<0.05).
PartⅢIntervention Study of Preventing the occurrence of Peritoneal Dialysis Ultrafiltration Failure
Materials and Methods
43 male SD rats of clean grade weighing 180-200g were used in the study. The uremia rats model was established by 5/6 nephrectomy and then from these uremia rats, we randomly established the peritoneal dialysis (PD) rats model. At last, there were 5 groups in this study:A:normal group (control group:n=8), B:uremia group (5/6 nephrectomy group:n=8), C:uremia peritoneal dialysis group (4.25% dialysized group:n=8), D1:the first treatment group with Endostar (10mg/kg treatment group: n=8), D2:the second treatment group with Endostar (40mg/kg treatment group:n=8). The rats from C, D1, D2 groups were given regular peritoneal dialysis. The catheters implanted in dialysis rats were tunneled subcutaneously to the neck and exchanged PD solutions per rat were kept in the abdominal cavity for 2 hours per day without anesthesia. The rats from D1, D2 groups accepted subcutaneous injection of Endostar during peritoneal dialysis period every other days, total administration 14 times. After regularly peritoneal dialysis for 28 days, tissue immunohistochemistry methods and reverse transcript polymerase chain reaction (RT-PCR) were applied to detect the mRNA and protein expressions of VEGF and in rats'peritoneal tissues of each group. Microvessel density (MVD) of peritoneal tissue was assessed using immunohistochemistry with CD34 monoclonal antibody. Statistical analysis was performed to compare with their expressions and co relationship in each group. Significance was defined as a=0.05.
Results
1. Base on normal group, the mRNA and protein expression of VEGF were significantly up-regulated in uremia group and uremia peritoneal dialysis group (P<0.05). Compared with uremia peritoneal dialysis group, the mRNA and protein expression of VEGF were significantly down-regulated in the first and second treatment groups with Endostar (P<0.05). Compared with the first treatment group with Endostar, the mRNA and protein expression of VEGF were significantly down-regulated in the second treatment group with Endostar (P<0.05)
2. Base on the normal group, MVD was up-regulated in uremia group and uremia peritoneal dialysis group (P<0.05). Compared with uremia peritoneal dialysis group, MVD was significantly down-regulated in the first and second treatment groups with Endostar (P<0.05). Compared with the first treatment group with Endostar, MVD was significantly down-regulated in the second treatment group with Endostar (P<0.05)
3. There was a positive correlation between VEGF and MVD in protein level (r=0.987, P=0.000)
Conclusions
1. The expression of VEGF、bFGF and ES was positive in peritoneal tissues both normal rats and human; the expression of VEGF、bFGF and ES was up-regulated by uremia circumstance and non-physiological compatibility peritoneal dialysis liquid.
2. The upregulation of VEGF and bFGF in peritoneal dialysis rat and patient peritoneum might participate in the increasement of the peritoneum neoangiogensis and then cause the incidence of ultrafiltration.
3. The protein level expression of ES was up-regulated by uremia circumstance and non-physiological compatibility peritoneal dialysis liquid. ES might play an important role in inhibitting peritoneum neoangiogensis
4. Recombinant human endostatin (Endostar) can effectively inhibit rat peritoneum neoangiogensis inducing by peritoneal dialysis, and the role of inhibit strength is related with the dose of the drug.
5. Recombinant human endostatin (Endostar) can inhibit rat peritoneum neoangiogensis by down-regulating the expression of VEGF in peritoneum.
引文
[1]Smit W, Schouten N, van den Berg N, et al. Analysis of the prevalence and causes of ultrafiltration failure during long-term peritoneal dialysis:a cross-sectional study [J]. PeritDial Int,2004,24:506-508.
[2]Fischbach M, Haraldsson B, Helms P, et al. The peritoneal membrane:a dynamic dialysis membrane in children [J]. Adv Perit Dial,2003,19:265-268.
[3]Szeto CC, Chow KM, Kwan BC, et al. The relationship between bone morphogenic protein-7 and peritoneal transport characteristics [J]. Nephrol Dial Transplant,2008, 23:2989-2994.
[4]Mujais S, Krediet R, Lindholm B, et al. Evaluation and management of ultra filtration problems in peritoneal dialysis. International Society for peritoneal Dialysis Ad Hoc Committee on Ultra filtration Management In Peritoneal Dialysis [J]. Perit Dial Int,2000, 20[Suppl4]:S5-21.
[5]Heimburger O, Waniewski J, Werynski A, et al. Peritoneal transport in CAPD Patients with Permanent loss of ultra filtration capacity [J]. Kidney int,1990,38:495-506.
[6]Smit W, Langedijk MJ, Schouten N, et al. A comparison between 1.36% and 3.86% glucose dialysis solution for the assessment of peritoneal membrane function [J]. Perit Dial Int, 2000,20:734,741.
[7]Williams JD, Craig KJ, Top ley N, et al. Morphologic changes in the peritoneal membrane of patients with renal disease [J]. J Am Soc Nephrol,2002,13:470-479.
[8]Margetts PJ, Gyorffy S, Kolb M, et al. Antiangiogenic and antifibroticgene therapy in a chronic infusion model of peritoneal dialysis in rats [J]. J Am Soc Nephrol,2002,13: 721-728.
[9]Honda K, Nitta K, Hofita S, et al. Accumulation of advanced glyeation end product sin the peritoneal vasculature of continuous ambulatory peritoneal dialysis patients with low ultra-filtration [J]. Nephrol Dial Transplant,1999,14(6):1541-1549.
[10]Mateijsen MA, van der Wal AC, Hendriks PM, et al. Vascular and interstitial changes in the peritoneum of CAPD patients with peritoneal sclerosis [J]. Perit Dial Int,1999,19(6): 517-525.
[11]De Vriese AS, Mortier S, Lameire NH. What happens to the peritoneal membrane in long-term peritoneal dialysis [J].Perit Dial Int,2001,21 [Suppl 3]:S9-S18.
[12]Vardhan A, Zweers MM, Gokal R, et al. A solutions portfolio approach in peritoneal dialysis [J]. Kidney Int,2003,64 [Suppl88]:S114-S123.
[13]De Vriese AS, Tilton RG, Stephan CC, et al. Vascular endothelial growth factor is essential for hyperglycemia-induced structural and functional alterations of the peritoneal membrane [J]. JAm Soc Nephrol,2001,12:1734-1741.
[14]Fabbrini P, Zareie M, ter Wee PM, et al. Peritoneal exposure model in the rat as a tool to unravel bio(in)compatibility of PDF [J]. Nephrol Dial Transplant,2006,21[Suppl 2]:8-11.
[15]Kim YL, Do J, Park SH, et al. Low glucose degradation products dialysis solution modulates the levels of surrogate markers of peritoneal inflammation, integrity, and angiogenesis:Preliminary report [J]. Nephrology (Carlton),2003,8 Suppl:S28-32.
[16]Nakamura S, Tachikawa T, Tobita K, et al. Role of advanced glycation end products and growth factors in peritoneal dysfunction [J]. Am J KidneyDis,2003,41 [Suppll]:S61-S67.
[17]Zareie M, De Vriese AS, Hekking LH, et al. Immunopathological changes in a uremic rat model for peritoneal dialysis [J]. Nephrol Dial Transp lant,2005,20:1350-1361
[18]Thornalley PJ. Advanced glycation end products in renal failure [J]. J Ren Nutr,2006,16: 178-184.
[19]Mohammad Zareiel, An S. De Vriese, Liesbeth H. P, et al. Immunopathological changes in a uremic rat model for peritoneal dialysis [J]. Nephrol Dial Transplant,2005,20:1350-136.
[20]Mujais S, Nolph K, Gokal R, et al. Evaluation and management of ultra filtration problems in peritoneal dialysis. International Society for Peritoneal Dialysis Ad Hoc Committee on Ultra filtration Management in Peritoneal Dialysis [J]. Perit Dial Int,2000,20(supple 4):S5-S21.
[21]Toi M, Matsumoto T, Bnado H. Vascular endothelial growth factor:its prognostic, predictive and therapeutic implications [J]. Lancet Oncol,2001,2:667-673.
[22]Combet S, Miyata I, Moulin P, et al. Vascular proliferation and enhanced expression of endothelial nitric oxide synthase in human perioneum exposed to long-term periotneal dialysis [J]. J Am Soc Nephrol.2000.11:717-728.
[23]Szeto CC, Chow KM, Wong TY, et al. Feasibility of resuming peritoneal dialysis after severe peritonitis and Tenchhoff catheter removal [J]. J Am Soc Nephrol 2002; 13:1040-5.
[24]Murakami M, Simons M. Fibroblast growth factor regulation of neovascularization [J]. Curr Opin Hematol.2008,15:215-220.
[25]Yan W, Bentley B, Shao R. Distinct Angiogenic Mediators are Required for bFGF and VEGF-induced Angiogenesis:the Role of Cytoplasmic Tyrosine Kinase c-Abl in Tumor Angiogenesis [J]. Mol Biol Cell,2008, May; 19:2278-2288.
[26]Horiguchi H, Jin L, Ruebel KH, et al. Regulation of VEGF-A,VEGFR-I, thrombospondin-1,-2, and-3 expression in a human pituitary cell line (HP75) by TGFbetal, bFGF, and EGF [J]. Endocrine,2004,24:141-146.
[27]Marcus VC, Sylvis S, Helmut K, et al. Basic fibroblast growth factor synthesis by human peritoneal mesothelial cells induction by interleukin-1 [J]. Am J Path,1999,155:1977-1984.
[28]O'Reilly MS, Boehm T, Shing Y, et al. Endostatin:An Endogenous inhibitor of angiogenesis and tumor growth [J]. Cell,1997,88:277-285.
[29]Wenzel D, Schmidt A, Riemann K, et al. Endostatin, the proteolytic fragment of collagen ⅩⅧ, induces vasorelaxation [J]. Cir-cul Res,2006,98:1203-1211.
[30]Rehn M, Veikola T, kukk-Valdre, et al. Interactin of endostatin with integrins implicated in angiogenesis [J]. Cell Biology,2001,98:1024-1029.
[31]Kim YM, Hwang S, Kim YM, et al. Endostatin blocks vascular endothelial growth factor-mediated signaling via direct interaction with KDR/Flk-1[J]. J Biol Chem,2002, 277(31):27872-27879.
[32]张晓东,钱家麒.一种简便的正常大鼠腹膜透析模型建立[J].中国血液净化,2005,4：326-328.
[33]Jimi T, Wakayama Y, Inouc M, et al. Aquporin 1:Examination of its expression and localization in normal human skeletal muscle tissue [J]. Cells Tissues Organ, 2006,184:181-187.
[34]Chadban SJ, Briganti EM, Kerr PG, et al. Prevalence of kidney damage in Australian adults: the Aus Diab Kidney Study [J]. J Am Soc Nephrol,2003,14:S131-S138.
[35]ShahabI, Khanna R, Nolph KD. Peritoneal dialysis or hemodialysis? A dilemma for the nephrologist [J]. Adv Perit Dial,2006,22:180-5.
[36]Nagy J. Peritoneal dialysis thrapy [J]. Kidney Int,1997:62(suppl):S105-7.
[37]Zweers MM, Splint LJ, Krediet RT, Struijk DG, et al. Ultrastructure of basement membranes of peritoneal capillaries in a chronic peritoneal infusion model in the rat [J]. Nephrol Dial Transplant,2001,16:651-4.
[38]De Vriese AS, Tilton RG, Stephan CC, et al. Vascular endothelial growth factor is essential for hyperglycemia-induced structural and functional alterations of the peritoneal membrane [J]. J Am Soc Nephrol,2001,12:1734-41.
[39]Zeltzer E, Klein O, Rashid G, et al. Intraperitoneal infusion of glucose-based dialysate in the rat--an animal model for the study of peritoneal advanced glycation end-products formation and effect on peritoneal transport [J]. Perit Dial Int,2000,20:656-61.
[40]Boulanger E, Grossin N, Wautier MP, et al. Mesothelial RAGE activation by AGEs enhances VEGF release and potentiates capillary tube formation [J]. Kidney Int,2007; 71(2):126-33.
[41]于青,赵东杰,姚建等.高糖、尿毒症血清对人腹膜间皮细胞VEGF表达的影响[J].中国血液净化,2005,7：379-392.
[42]Aquilera A, Aroeira LS, Ramirez-Huesca M, et al. Effects of rapamycin on the epithelial-to-mesenchymal transition of human peritoneal mesothelial cells [J]. Int J Artif Organs. 2005,28(2):164-9.
[43]Aroeira LS, Aquilera A, Selgas R, et al. Mesenchymal conversion of mesothelial cells as a mechanism responsible for high solute transport rate in peritoneal dialysis:role of vascular endothelial growth factor [J]. Am J Kidney Dis.2005,46(5):938-48.
[44]郭群英,李晓艳,余学清等.腹膜透析液诱导结缔组织生长因子在大鼠腹膜间皮细胞表达[J].中华肾脏病杂志,2006,22(2)：114-118.
[45]陆福明,顾亢霞,郭晓敏等.终末期糖基化产物在尿毒症患者血清中的水平及血管壁和腹膜上的表达[J].中华肾脏病杂志,2000,16：147-151.
[46]Honda K, Hamada C, Nakayama M, et al. Impact of uremia, diabetes, and peritoneal dialysis itself on the pathogenesis of peritoneal sclerosis:a quantitative study of peritoneal membrane morphology [J]. Clin J Am Soc Nephrol,2008,3:720-8.
[47]Nakayama M, Yoshimura K, Maruyama Y, et al. Possible involvement of cross-linking advanced glycation endproducts in long-term CAPD peritoneal degeneration [J]. Nephrol Dial Transplant,2004,19:1664-1665.
[48]Chin D, Boyle GM, Parsons PG, et al. What is transforming growth factor-beta (TGF-beta) [J]. Br J Plast Surg,2004,57:215-221.
[49]Groppe J, Hinck CS, Samavarchi-Tehrani P, et al. Cooperative assembly of TGF-beta superfamily signaling complexes is mediated by two disparate mechanisms and distinct modes of receptor binding [J]. Mol Cell,2008,29:157-168.
[50]Wu XL, Zeng WZ, Jiang MD, et al. Effect of Oxymatrine on the TGF beta-Smad signaling pathway in rats with CCl(4)-induced hepatic fibrosis [J]. World J Gastroenterol,2008,14: 2100-2105.
[51]Selgas R, Bajo A. Epithelial-to-mesenchymal transition of mesothelial cell-its role in the response of the peritoneum to dialysis [J]. Nephrol Dial Transplant,2006,21:112-117.
[52]Tanabe K, Maeshima Y, Ichinose K, et al. Endostatin peptide, an inhibitor of angiogenesis, prevents the progression of peritoneal sclerosis in a mouse experimental model [J]. Kidney Int,2007,71:227-238.
[53]刘凡,王小宜,刘运生等.垂体腺瘤VEGF、bFGF和内皮抑素：mRNA表达与血管生成的关系[J].医学临床研究,2006,23：1172-1174.
[54]Heimburger O, Wang T, Lindholm B. Alterations in water and solute transport with time on peritoneal dialysis [J]. Perit Dial Int 1999; 19(2):S83-S90.
[55]Hohenester E, Sasaki T, Olsen BR, et al. Crystal structure of the angiogenesis inhibitor endostatin at 1.5A resolution [J]. Embo J,1998,17:1656-1664.
[56]Gaetzner S, Deckers MM, Stahl S, et al. Endostatin's heparin sulfate-binding site is essential for inhibition of angiogenesis and enhances in situ binding to capillary-like structure in bone explants [J]. Matrix Biol,2005,23:557-561.
[57]Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis [J]. Cell,1996,86:353-364.
[58]Io H, Hamada C, Ro Y, et al. Morphologic changes of peritoneum and expression of VEGF in encapsulated peritoneal sclerosis rat models [J]. Kidney Int,2004,65:1927-1936.
[1]El Nahas AM, Belb AK. Chronic Kidney disease:the global challenge [J]. Lancet, 2005,365:331-340.
[2]Lysaght MJ. Maintenance dialysis population dynamics current trends and long-term implications [J]. JAM Soc Nephrol,2002,13:37-40.
[3]王海燕.译后评论：我国慢性肾脏病的新数据及其警示[J].英国医学杂志(中文版),2006,9(3)：136.
[4]Mujais S, Nolph K, Gokal R, et al. Evaluation and management of ultrafiltration problems in peritoneal dialysis. International Society for Peritoneal Dialysis Ad Hoc Committee on Ultrafiltration Management in Peritoneal Dialysis [J]. Perit Dial Int,2000,20(supple 4):S5-S21.
[5]Toi M, Matsumoto T, Bnado H. Vascular endothelial growth factor:its prognostic, predictive and therapeutic implications [J]. Lancet Oncol,2001,2:667-673.
[6]Combet S, Miyata I, Moulin P, et al. Vascular proliferation and enhanced expression of endothelial nitric oxide synthase in human perioneum exposed to long-term periotneal dialysis [J]. J Am Soc Nephrol,2000,11:717-728.
[7]Szeto CC, Chow KM, Wong TY, et al. Feasibility of resuming peritoneal dialysis after severe peritonitis and Tenchhoff catheter removal [J]. J Am Soc Nephrol 2002; 13:1040-5.
[8]Murakami M, Simons M. Fibroblast growth factor regulation of neovascularization [J]. Curr Opin Hematol,2008,15:215-20.
[9]Yan W, Bentley B, Shao R. Distinct Angiogenic Mediators are Required for bFGF and VEGF-induced Angiogenesis:the Role of Cytoplasmic Tyrosine Kinase c-Abl in Tumor Angiogenesis [J]. Mol Biol Cell,2008, May; 19:2278-88.
[10]Horiguchi H, Jin L, Ruebel KH, et al. Regulation of VEGF-A,VEGFR-I, thrombospondin-1,-2, and -3 expression in a human pituitary cell line (HP75) by TGFbetal, bFGF, and EGF [J]. Endocrine,2004,24:141-146.
[11]Marcus VC, Sylvis S, Helmut K, et al. Basic fibroblast growth factor synthesis by human peritoneal mesothelial cells induction by interleukin-1 [J]. Am J Path,1999,155:1977-1984.
[12]O'Reilly MS, Boehm T, Shing Y, et al. Endostatin:An Endogenous inhibitor of angiogenesis and tumor growth [J]. Cell,1997,88:277-285.
[13]Wenzel D, Schmidt A, Riemann K, et al. Endostatin, the proteo-lytic fragment of collagen XVIII, induces vasorelaxation [J]. Cir-cul Res,2006,98:1203-1211.
[14]Rehn M, Veikola T, kukk-Valdre, et al. Interactin of endostatin with integrins implicated in angiogenesis [J]. Cell Biology,2001,98:1024-1029.
[15]Nagy J. Peritoneal dialysis thrapy[J]. Kidney Int,1997:62(suppl):S105-7.
[16]Smit W, Schouten N, van den Berg N, et al. Analysis of the prevalence and causes of ultrafiltration failure during long-term peritoneal dialysis:a cross-sectional study [J]. Perit Dial Int,2004,24:506-508.
[17]Chadban SJ, Briganti EM, Kerr PG, et al. Prevalence of kidney damage in Australian adults: the Aus Diab Kidney Study [J]. J Am Soc Nephrol,2003,14:S131-S138.
[18]ShahabI, Khanna R, Nolph KD. Peritoneal dialysis or hemodialysis? A dilemma for the nephrologist [J]. Adv Perit Dial,2006,22:180-5.
[19]Zareie M, Fabbrini P, Hekking LH, et al. Novel role for mastcells in omental tissue remodeling and cell recruitment in experimental peritoneal dialysis [J]. J Am Soc Nephrol, 2006,17:3447-3457.
[20]赵占正,刘章锁,李艳等.内皮抑素在大鼠腹膜的表达及其与腹膜血管新生的关系[J],中华肾脏病杂志,2009,6：437-440.
[21]Boulanger E, Grossin N, Wautier MP, et al. Mesothelial RAGE activation by AGEs enhances VEGF release and potentiates capillary tube formation [J]. Kidney Int,2007,71: 126-133.
[22]Combet S, Miyata I, Moulin P, et al. Vascular proliferation and enhanced expression of endothelial nitric oxide synthase in human perioneum exposed to long-term periotneal dialysis [J]. J Am Soc Nephrol,2000.11:717-728.
[23]Szeto CC, Chow KM, Wong TY, et al. Feasibility of resuming peritoneal dialysis after severe peritonitis and Tenchhoff catheter removal [J]. J Am Soc Nephrol,2002; 13:1040-5.
[24]于青,赵东杰,姚建等.高糖、尿毒症血清对人腹膜间皮细胞VEGF表达的影响[J].中国血液净化,2005,7：379-392.
[25]Aquilera A, Aroeira LS, Ramirez-Huesca M, et al. Effects of rapamycin on the epithelial-to-mesenchymal transition of human peritoneal mesothelial cells [J]. Int J Artif Organs, 2005;28(2):164-9.
[26]Aroeira LS, Aquilera A, Selgas R, et al. Mesenchymal conversion of mesothelial cells as a mechanism responsible for high solute transport rate in peritoneal dialysis:role of vascular endothelial growth factor [J]. Am J Kidney Dis,2005;46(5):938-48.
[27]郭群英,李晓艳,余学清等.腹膜透析液诱导结缔组织生长因子在大鼠腹膜间皮细胞表达[J].中华肾脏病杂志,2006,22(2)：114-118.
[28]Murakami M, Simons M. Fibroblast growth factor regulation of neovascularization [J]. Curr Opin Hematol,2008,15:215-20.
[29]Yan W, Bentley B, Shao R. Distinct Angiogenic Mediators are Required for bFGF and VEGF-induced Angiogenesis:the Role of Cytoplasmic Tyrosine Kinase c-Abl in Tumor Angiogenesis [J]. Mol Biol Cell,2008, May; 19:2278-88.
[30]陆福明,顾亢霞,郭晓敏等.终末期糖基化产物在尿毒症患者血清中的水平及血管壁和腹膜上的表达[J].中华肾脏病杂志,2000,16：147-151.
[31]Nakayama M, Yoshimura K, Maruyama Y,et al. Possible involvement of cross-linking advanced glycation endproducts in long-term CAPD peritoneal degeneration [J]. Nephrol Dial Transplant,2004,19:1664-1665.
[32]Chin D, Boyle GM, Parsons PG, et al. What is transforming growth factor-beta (TGF-beta)? [J]. Br J Plast Surg,2004,57:215-21.
[33]Selgas R, Bajo A, et al. Epithelial-to-mesenchymal transition of mesothelial cell—its role in the response of the peritoneum to dialysis [J]. Nephrol Dial Transplant,2006,21:112-7.
[34]Wenzel D, Schmidt A, Riemann K, et al. Endostatin, the proteo-lytic fragment of collagen XVIII, induces vasorelaxation [J]. Cir-cul Res,2006,98:1203-1211.
[35]Kim YM, Hwang S, Kim YM, et al. Endostatin blocks vascular endothelial growth factor-mediated signaling via direct interaction with KDR/Flk-1[J]. J Biol Chem,2002, 277(31):27872-27879.
[36]Tanabe K, Maeshima Y, Ichinose K, et al. Endostatin peptide, an inhibitor of angiogenesis, prevents the progression of peritoneal sclerosis in a mouse experimental model [J]. Kidney Int,2007,71:227-238.
[37]刘凡,王小宜,刘运生等.垂体腺瘤VEGF、bFGF和内皮抑素nRNA表达与血管生成的关系[J].医学临床研究,2006,23：1172-1174.
[38]Aroeira LS, Aguilera A, Selgas R, et al. Mesenchymal conversion of mesothelial Cells as a mechanism responsible for high solute transport rate inperitonealdialysis:role of vascular endothelial growth factor [J]. Am J Kidney Dis,2005,46(5):938-948.
[39]Walgenbach KJ, Gorospe JR, Gratas C. A potential role for mast cells in the release of bFGF from normal myocytes during angiogenesis in vivo [J]. Journal of investigative surgery,2002,15(3):153.
[40]Nissen N N, Polverini P J, Koch A E, et al. Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing [J]. Am J Pathol,1998, 152(6):1445-1452.
[41]Ryuto M, Ono M, Izumi H, et al. Induction of vascular endothelial growth factor by tumor necrosis factor alpha in human glioma cells [J]. Possible roles of SP-1 1996,271(45):28220.
[42]Pepper MS, Mandriota SJ, Vassalli JD, et al. Angiogenesis regulating cytokines:actions and interactions [J]. Curr Top Microbiol Immunol,1996,213:31.
[43]Sasaki T, Larsson H, Kreuger J, et al. Stmcture basis and potential of heparin/hepatan sulfate binding to the angiogenesie inhibitor endostatin [J]. Embo J,1999,18(22): 6240-6248.
[44]Rehn M, Veikola T, kukk-Valdre, et al. Interactin of endostatin with integrins implicated in angiogenesis [J]. Cell Biology,2001,98:1024-1029.
[45]Hohenester E, Sasaki T, Olsen BR, et al. Crystal structure of the angiogenesis inhibitor endostatin at 1.5A resolution [J]. Embo J,1998,17:1656-1664.
[46]Gaetzner S, Deckers MM, Stahl S, et al. Endostatin's heparin sulfate-binding site is essential for inhibition of angiogenesis and enhances in situ binding to capillary-like structure in bone explants [J]. Matrix Biol,2005,23:557-561.
[47]Hanahan D, Folkman J. Patterns and emerging mechanisms of the an gio-genicseich during tumorigenesis [J]. Cell,1996,86(3):353-364.
[1]Yan W, Bentley B, Shao R. Distinct Angiogenic Mediators are Required for bFGF and VEGF-induced Angiogenesis:the Role of Cytoplasmic Tyrosine Kinase c-Abl in Tumor Angiogenesis [J]. Mol Biol Cell,2008,19(5):2278-2288.
[2]Horiguchi H, Jin L, Ruebel KH, et al. Regulation of VEGF,VEGFR-I, thrombospondin-1,-2, and-3 expression in a human pituitary cell line (HP75) by TGFbetal, bFGF, and EGF [J]. Endocrine,2004;24:141-146.
[3]Marcus VC,Sylvis S,Helmut K,et al.Basic fibroblast growth factor synthesis by human peritoneal mesothelial cells induction by interleukin-1 [J].Am J Path,1999,155:1977-1984.
[4]袁江姿,钱家麒,方炜等.尿毒症腹透对大鼠腹膜形态和功能的影响[J].上海交通大学学报(医学版),2007,27：1189-1192.
[5]Weidner N. Intratumor micro vessel density as prognostic factor in cancer [J]. Am J Pathol, 1995,147:9-11.
[6]Zareie M, De Vriese AS, Hekking LH, et al. Immunopathological changes in a uraemic rat model for peritoneal dialysis [J]. Nephrol Dial Transplant,2005; 20 (7):1350-1361.
[7]Ho-dac-Pannekeet MM, Atasever B, Struijk DG, et al. Analysis of ultrafiltration failure in peritoneal dialysis patients by means of standard peritoneal permeability analysis [J]. Perit Dial Int,1997; 17:144-150.
[8]Jorres A, Bender TO, Finn A et al. Biocompatibility and buffers:effect of bicarbonate-buffered peritoneal dialysis fluids on peritoneal cell function [J]. Kidney Int,1998;54(6): 2184-2193.
[9]Stigant CE, Bargman JM. What's new in peritoneal dialysis:biocompatibility and continuous flow peritoneal dialysis [J]. Curr Opin Nephrol Hypertens,2002; 11 (6):97-602.
[10]Lopez-Cabrera M, Aguilera A, Aroeira LS et al. Ex vivo analysis of dialysis effluent-derived mesothelial cells as an approach to unveiling the mechanism of peritoneal membrane failure [J]. Perit Dial Int,2006; 26(1):26-34.
[11]Combet S, Miyata T, Moulin P et al. Vascular proliferation and enhanced expression of endothelial nitric oxide synthase in human peritoneum exposed to long-term peritoneal dialysis [J]. J Am Soc Nephrol,2000; 11(4):717-728.
[12]Okada-Ban M, Thiery JP, Jouanneau J. Fibroblast growth factor-2 [J]. Int J Biochem Cell Biel,2000;32(3):263-267.
[13]Hohenester E, Sasaki T, Olsen BR, et al. Crystal structure of the angiogenesis inhibitor endostatin at 1.5A resolution [J]. Embo J,1998;17:1656-1664.
[14]Bellini MH, Coutinho EL, Filgueiras TC, et al. Endostatin expression in the murine model of ischaemia/reperfusion-induced acute renal failure [J]. Nephrology (Carlton),2007; 12: 459-465.
[15]Ai RZ, Wu Y, Liu Q, et al. Suppression of lung cancer in murine model:treated by combination of recombinant human endostsatin adenovirus with low-dose cisplatin [J]. Exp Clin Cancer Res,2009,5:28-31.
[16]Retsky MW, Hrushesky WJ, Gukas ID, et al. Hypothesis:primary antiangiogenic method proposed to treat early stage breast cancer [J]. BMC Cancer,2009, Jan 8; 9:7.
[17]汪涛,王英.腹膜透析的现状[J].医师进修杂志,2002,25(2)：13-15.
[18]Liem YS, Wong JB, Hunink MG, et al. Comparison of hemodialysis and peritoneal dialysis survival in the Netherlands [J]. Kidney Int,2007,71(2):153-158.
[19]Vonesh EF, Snyder JJ, Foley RN, et al. The differential impact of risk factors on mortality in hemodialysis and peritoneal dialysis [J]. Kidney Int,2004; 66 (6):2389-2401.
[20]Smit W, Schouten N, van den Berg N, et al. Analysis of the prevalence and causes of ultrafiltration failure during long-term peritoneal dialysis:a cross-sectional study [J]. Perit Dial Int,2004;24:506-508.
[21]Plum J, Hermann S, Fussholler A, et al. Peritoneal sclerosis in peritoneal dialysis patients related to dialysis settings and peritoneal transport properties [J]. Kidney Int,2001,78 Suppl:S42-7.
[22]Van Westrhenen R, Zweers MM, Kunne C, et al. A pyruvate-buffered dialysis fluid induces less peritoneal angiogenesis and fibrosis than a conventional solution [J]. Perit Dial Int, 2008; 28(5):487-96.
[23]Parikova A, Smit W, Struijk DG, et al. Analysis of fluid transport pathways and their determinants in peritoneal dialysis patients with ultrafiltration failure [J]. Kidney Int,2006; 70(11):1988-94.
[24]Hanahan D, Folkman J. Patterns and emerging mechanisms of the an-giogenic switch during tumorigenesis [J]. Cell,1996,86:353-364.
[25]Yoshio Y, Miyazaki M, Abe K, et al. TNP-470,an angiogenesis inhibitor, suppresses the progression of peritoneal fibrosis in mouse experimental model [J]. Kidney Int,2004; 66: 1677-1685.
[26]Senger DR, Galli SJ, Dvorak AM, et al. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid [J]. Science,1983,219(4587):983-985.
[27]Leung DW, Cachianes G, Kuang WJ, et al. Vascular endothelial growth factor is a secreted angiogenic mitogen [J]. Science,1989;246:1306.
[28]Nowak DG, Woolard J, Amin EM, et al. Expression of pro-and anti-angiogenic isoforms of VEGF is differentially regulated by splicingand growth factors [J]. Cell Sci,2008,121: 3487-3495.
[29]awasaki T, Kitsukawa T, Bekku Y, et al. A requirement for neuropilin-1 in embryonic vessel formation [J]. Development,1999,126:4895-4902.
[30]Boulanger E, Grossin N, Wautier MP, et al. Mesothdial RAGE activation by AGEs enhances VEGF release and potentiates capillary tube formation [J]. Kidney Int,2007, 71(2):126-133.
[31]Combet S, Miyata T, Moulin P, et al. Vascular proliferation and enhanced expression of endothelial nitric oxide synthase in human peritoneum exposed to long-term peritoneal dialysis [J]. J Am Soc Nephrol,2000, 11(4):717-728.
[32]张晓东,钱家麒.一种简便的正常大鼠腹膜透析模型建立[J].中国血液净化,2005,4：326-328.
[33]O'Reilly MS, Boehm T, Folkman J, et al. Endostatin:an endogenous inhibitor of angiogenesis and tumor growth [J]. Cell,1997,88(2):277-285.
[34]Hohenester E, Sasaki T, Olsen BR, et al. Crystal structure of the angiogenesis inhibitor endostatin at 1.5 A resolution [J]. EMBO J,1998,17(6):656-1664.
[35]Folkman J. Antiangiogenesis in cancer therapy-endostatin and its mechanisms of action [J]. Exp. Cell Res,2006,3(12):594-607.
[36]柏树令,赵丹.CD34抗原的生物学特性及其临床应用[J].解剖科学进展,2005,11(1)：54-60.
[37]Abdollahi A, Hahnfeldt P, Maercker C, et al. Endostatin's antiangiogenic signaling network [J]. Mol. Cell,2004,13,649-663.
[38]Nyberg P, Xie L, Kalluri R. Endogenous inhibitors of angiogenesis [J]. Cancer Res,2005, 65,3967-3979.
[39]Kim Y M, Jang J W, Lee O H, et al. Endostatin inhibits endothelial and tumor cellular invasion by blocking the activation and catalytic activity of matrix metalloproteinase [J]. Cancer Res,2000,60(19):5410-5413.
[40]Rehn M, Veikkola T, Kukk-Valdre E, et al. Interaction of endostatin with integrins implicated in angiogenesis [J]. Proc Natl Acad Sci USA,2001,98(3):1024-1029.
[41]Kim Y M, Hwang S, Kim Y M, et al. Endostatin blocks vascular endothelial growth factor-mediated signaling via direct interaction with KDR/Flk-1 [J]. J Biol Chem,2002, 277(31):27872-27879.
[1]E1 Nahas AM, Belb AK. Chronic Kidney disease:the global challenge [J]. Lancet,2005; 365:331-340
[2]Lysaght MJ. Maintenance dialysis population dynamics current trends and long-term implications[J].J Am Soc Nephrol,2002;13:37-40
[3]Mato D, Alvarez-Aguilar C, Castaneda-Limones R, et al. Prevalence of chronic kidney disease in an urban Mexican population[J]. Kidney Int,2005;68(Suppl97); 11-17
[4]王海燕.译后评论：我国慢性肾脏病的新数据及其警示[J].英国医学杂志(中文版),2006；9(3)：136.
[5]Laucapis A, Keown P, Pus N, et al. A study of the quality of life and cost-utility of renal translation[J]. Kidney Int,1999;50:235-242.
[6]文吉秋,纪玉莲,郑智华,等.血液透析、腹膜透析和肾移植的成本-效果分析[J].中华肾脏病杂志,2005;21(10)：616-619
[7]Liem YS, Wong JB, Hunink MG, et al. Comparison of hemodialysis and peritoneal dialysis survival in the Netherlands [J]. Kidney Int,2007,71(2):153-158.
[8]Vonesh EF, Snyder JJ, Foley RN, et al. The differential impact of risk factors on mortality in hemodialysis and peritoneal dialysis [J]. Kidney Int,2004; 66(6):2389-2401.
[9]王峦,程晓明,张璐莹等.杭州市腹膜透析和血液透析治疗费用与疗效的比较研究[J].中国卫生资源,2009,12(3)：129-131.
[10]Musphy SW, Foley RN, Barrett BJ, et al. Comparative mortality of hemodialysis and peritoneal dialysis in Canada[J]. Kidney Int,2000,57:1720
[11]US Renal Data System, Exceptis from the USRDS 2000 Annual Data Re-port:Atlas of end-stage renal disease in the United States[J]. Am J Kidney Dis,2000; 36 (Suppl 2):S1
[12]Nagy J. Peritoneal dialysis therapy[J]. Kidney Int,1997:62(suppl):S105-7.
[13]Smit W, Schouten N, van den Berg N, et al. Analysis of the prevalence and causes of ultrafiltration failure during long-term perito-neal dialysis:a cross-sectional study[J]. Perit Dial Int,2004,24:506-508.
[14]Heimburger O, Wanjewski J,Werynski A,et al. Peritoneal transport in CAPD patients with permanent loss of ultrafltration capacity[J]. Kidney Int 1990,38:495-506.
[15]Ho-dac-Pannekeet MM, Atasever B, Struijk DG, et al.A nalysis of ultrafiitration failure in peritoneal dialysis patients by means of standard peritoneal permeability analysis[J]. Perit Dial Int,1997,17:144-150
[16]Mujais S, Nolph K, Gokal R, et al. Evaluation and management of ultrafiltration problems in peritoneal dialysis. International Society for Peritoneal Dialysis Ad Hoc Committee on Ultrafiltration Management in Peritoneal Dialysis[J]. Perit Dial Int,2000,20(supple 4):S5-S21.
[17]Williams JD, Craig KJ, Top ley N, et al. Morphologic changes in the peritoneal membrane of patients with renal disease[J]. J Am Soc Nephrol,2002,13:470-479.
[18]Mortier S, De Vriese As, Vanol, et al. Hemodynamic effects of peritoneal dialyse; solutions on the rat peritoneal membrane:Role of acidity, buffer choice, glucose concentration, and glucose degradation products[J]. J Am Soc Nephrol,2002,13:480-489
[19]Ates K, Koc R, Nergizoglu G, et al. The longitudinal effect of a single peritonitis episode on peritoneal membrane transport in CAPD patients[J]. Perit Dial Int,2000,20:220-226
[20]郭群英,李晓艳,余学清等.腹膜透析液诱导结缔组织生长因子在大鼠腹膜人腹膜间皮细胞AQP和FGF对腹膜超滤影响的实验研究间皮细胞表达[J].中华肾脏病杂志,2006,22(2)：114-118.
[21]于青,赵东杰,徐琦等.高糖、尿毒症血清对人腹膜间皮细胞VEGF表达的影响[J].中国血液净化,2005,4(7)：379-380.
[22]Davies SJ, Bryan J, Phillips L, et al. Longitudinal changes in peritoneal kinetics:The effects of peritoneal dialysis and peritonitis[J]. Nephrol Dial Transplant,1996,11:498-506.
[23]Zweers MM, Splint LJ, Krediet RT, et al. Ultrastructure of basement membranes of peritoneal capillaries in a chronic peritoneal infusion model in the rat [J]. Nephrol Dial Transplant,2001,16:651-654.
[24]Heimburger 0, Wang T, Lindholm B. Alterations in water and solute transport with time on peritoneal dialysis [J]. Perit Dial Int,1999,19 [Suppl 2]:583-590.
[25]Brownlee M. Biochemistry and molecular cell biology of diabetic complications [J]. Nature,2001;414:813-820
[26]De Vriese AS,Moritier S,Lameire NH.Glucotoxicity of the peritoneal membrane:the case for VEGF[J].Nephrol Dial Transplant,2001;16:2299-2302
[27]Zareie M, Keuning ED, ter Wee PM, et al. Improved biocompatibility of bicarbonate/ lactate-buffered PDF is not related to Ph[J]. Nephrol Dial Transplant,2006,21(1): 208-216.
[28]PENG Wei-sheng, ZHOU Qiao-ling, YU Xue-qing, et al. Effects and significance of different glucose concentrations and LPS on the expression of VEGF and vascular proliferation in the peritoneal membrane of dialysis rat [J]. China Journal of Modern Medicine,2007,17(17):2085-2088.
[29]Mateijsen MA, vander Wal AC, Hendriks PM, et al. Vascular and interstitial changes in the peritoneum of CAPD patients with peritoneal sclerosis [J]. Perit Dial Int,1999,19(6): 517-525.
[30]Tauer A, Knerr T, Niwa T, et al. In vitro formation of N(epsilon)-(carboxymethyl)-lysine and imidazolones under conditions similar to continuous ambulatory peritoneal dialysis [J]. Biochem Biophys Res Commun,2001;280:1408-1414.
[31]Witowski J, Wisniesska J, Korybalska D, et al. Prolonged exposure to glucose degradation products impairs viability and function of human peritoneal mesothelial cells [J]. J Am Noc Nephrol,2001,12:2434-2441.
[32]Inagi R, Miyata M, Yamamoto R, et al. Glucose degradation product methylglyoxal enhances the production of vascular endothelial growth factor in peritoneal cells:role in the functional and morphological alterations of peritoneal membranes in peritoneal dialysis [J]. FEBS Lett,1999;463(3):260-264.
[33]Davies SJ, Phillips L, Naish PF, et al. Peritoneal Glucose exposure and changes in membrane solute transport with time on peritoneal dialysis [J]. J Am Soc Nephrol,2001,12: 1046-1051.
[34]Selgas R, Bajo MA, Castro MJ, et al. Risk factors responsible for ultrafiltration failure in early stages of peritoneal dialysis [J]. Perit Dial Int,2000; 20:631-636.
[35]Sakamoto N, Sugimura K, Kawashima H, et al. Infulence of glucose and inflammatory eytokines on TGF-beta 1 and CTGF mRNA expression in human peritoneal mesothelial cells [J]. Int J Mol Med,2005,15(6):907-911.
[36]Rodrigues AS, Martins M, Korevaar JC, et al. Evaluation of peritoneal transport and membrane status in peritoneal dialysis:focus on incident fast transporters [J]. Am J Nephrol,2007,27:84-91.
[37]Reyes MJ, Bajo MA, Hevia C, et al. Inherent high peritoneal transport and ultrafiltration deficiency:their mid-term clinical relevance [J]. Nephrol Dial Transplant,2007,22:218-23.
[38]Lai KN, Lai KB, Lam CW, et al. Changes of cytokine profiles during peritonitis in patients on continuous ambulatory peritoneal dialysis [J]. Am J Kid Disease,2000,35:644-652.
[39]Combet S, Van Landschoot M, Moulin P, et al. Regulation of aquqporin-1 and nitric oxide synthase isoforms in a rat model of acute peritonitis [J]. J Am Soc Nephrol,1999,10: 2185-2196.
[40]Zareie M, De Vriese AS, Hekking LH, et al. Immunopathological changes in a uraemic rat model for peritoneal dialysis [J]. Nephrol Dial Transplant,2005,20(7):1350-1361.
[41]Miyata T, van Ypersele, de Strihou C, et al. Alterations in nonenzymatic biochemistry in uremia:origin and significance of carbonyl stress"in long-term uremic complications [J]. Kidney Int,1999,55(2):389-399.
[42]Kakuta T, Tanaka R, SatohY, et al. Pyridoxamine improves functional structural and biochemical alterations of peritoneal membranes in uremic peritoneal dialysis rats [J]. Kidney Int,2005,68(3):1326-1336.
[43]YUAN Jiang-z, QIAN Jia-qi, FANG Wei-sheng, et al. Morphologic and functional alterations of peritoneum in uremic rats undergoing peritoneal dialysis [J]. Journal of Shanghai Jiaotong University(Medical Science),2007,27 (10):1189-1992.
[44]Combet S, Ferrier ML, Van Landschoot M, et al.Chronic uremia induces permeability changes, increased nitric oxide synthase expression, and structural modifications in the peritoneum[J].J Am Soc Nephrol,2001;12:2146-2157
[45]Heaf JG, Sarac S, Afzal S. A high peritoneal large pore fluid flux causes hypoalbuminaemia and is a risk factor for death in peritoneal dialysis patients [J]. Nephrol Dial Transplant,2005,20:2194-2201
[46]Margetts PJ, Gyorffy S, Kolb M, et al. Antiangiogenic and antifibrotic gene therapy in a chronic infusion model of peritoneal dialysis in rats [J]. J Am Soc Nephrol,2002,13: 721-728.
[47]郭吴,李学军.细胞膜上的水通道--2003年诺贝尔化学奖工作介绍[J].生理科学进展,2007,38(3)：283.288.
[48]Lai KN, Li FK, Lan HY, et al. Expression of aquaporin-1 in human peritoneal mesothelial cells and its upregulation by glucose in vitro [J]. J Am Soc Nephrol,2001,12(5):1036-1045.
[49]方炜,钱家麒,余志远等.水孔蛋白-1在人腹膜组织的表达以及腹膜透析对其表达的影响[J].中华肾脏病杂志,2003,19(1)：29-33.
[50]Schoenicke G, Diamant R, Donner A, et al. Histochemical distribution and expression of aquaporin-1 in the peritoneum of patients undergoing peritoneal dialysis:Relation to peritoneal transport [J]. Am J Kidney Dis,2004,44(1):146-154.
[51]Ni J, Verbavatz JM, Rippe A, et al. Aquaporin 1 plays an essentiai role in water permeability and ultrafiltration during peritoneal dialysis [J]. Kidney Int,2006,69(9): 1518-1525.
[52]Goffin E, Combet S, Jamar F, et al. Expression of aquaporin-1 in a long-term peritoneale dialysis patient with impaired transcellular water transport [J]. Am J Kid Disease,1999, 33:383-388.
[53]Aroeira LS, Aguilera A, Sanchez Tomero JA, et al. Epithelial to mesenchymal transition and peritoneal membrane failure in peritoneal dialysis patients:pathologic significance and potential therapeutic interventions[J]. J Am Soc Nephrol,2007,18(7):2004-2013.
[54]Zarrinkalma KH, Stanley JM, Gray J, et al. Connectives tissue growth factor and its regulation in the peritoneal dialysis patitoneal diyalsis patients [J]. Kidney Int,2003, 64(1):331-338.
[55]Yao Q, Qian JQ, Lin XH, et al. Inhibition of the effect of high glucose on the expression of smad in human peritoneal mesothelial cells[J].Int J Artif Organs,2004,27:828-834.
[56]Mactier RA, Khanna R, Twardowski ZJ, et al. Ultrafiltration failure in continuous ambulatory peritoneal dialysis due to excessive peritoneal cavity lymphatic absorption [J]. Am J Kidney Dis,1987,10:461-466
[57]Flessner MF.Changes in the peritoneal interstitium and their effect on peritoneal transport [J]. Perit Dial Int,1999,19[Suppl 2]:77-82.
[58]刘宏富.长期腹膜透析超滤衰竭的预防及处理[J].中国中西医结合肾脏病杂志,2002,3：620-622.
[59]De Vriese AS, Tilton FG,Stephan CG.,et al..Diabetes induced microvascular proliferation and hypermeability in the peritoneum.role of vascular endothelial growth factor [J]. J Am Soc Nephrol,2001,12:1734-1741.
[60]Hanahan D, Folkman J. Patterns and emerging mechanisms of the an-giogenic switch during tumorigenesis [J]. Cell,1996,86:353-364.
[61]Tepper OM, Galiano RD, Kalka C, et al. Endothelial progenitor cells:the promise of vascular stem cells for plastic surgery [J]. Plast Reconstr Surg,2003,111:846.
[62]Bdolah Y, Sukhatme VP, Karumanchi SA.Angiogenic imbalance in the patho-physiology of preeclampsia:newer insights [J]. Semin Nephrol,2004;24:548-556.
[63]Senger DR, Galli SJ, Dvorak AM, et al. Tumor cells secrete a vascular per-meability factor that promotes accumulation of ascites fluid [J]. Science,1983; 219(4587):983-985.
[64]Leung DW, Cachianes G, Kuang WJ, et al. Vascular endothelial growth factor is a secreted angiogenic mitogen [J]. Science,1989,246:1306.
[65]Risau W. Mechanisms of angiongenesis [J]. Nature,1997,386(6626):671-674.
[66]Lei J, Jiang A, Pei D, et al. Identification and characterization of a new splicing variant of vascular endothelial growth factor:VEGF183 [J]. Biochim Biophys Acta,1998,1443 (3):400-406.
[67]Huang Z, Bao SD. Roles of main pro-and anti-angiogenic factors in tumor angiogenesis [J]. World J Gastroenterol,2004,10:463-470.
[68]Matsumoto C, Claesson WL. Sci-STKE,2001; 2001 (112):RE21.
[69]Eremina V, Sood M, Haigh J, et al. Glomerular-specific alterations of VEGF expression lead to distinct congenital and acquired renal diseases [J]. J Clin Invest,2003,111 (5):707-716.
[70]Ferrara N, Gerber HP, Le Couter J. The biology of VEGF and its receptors [J]. Nat Med,2003,9 (6):669-676.
[71]Boulanger E, Grossin N, Wautier MP, et al.Mesothdial RAGE activation by AGEs enhances VEGF release and potentiates capillary tube formation [J]. Kidney Int, 2007,71(2):126-133.
[72]Combet S, Miyata T, Moulin P, et al. Vascular proliferation and enhanced expression of endothelial nitric oxide synthase in human peritoneum exposed to long-term peritoneal dialysis [J]. J Am Soc Nephrol,2000, 11(4):717-728.
[73]Pecoits-Filho R, Araujo MR, Lindholm B, et al. Plasma and dialysate IL-6 and VEGF concentrations are associated with high peritoneal solute transport rate [J]. Nephrol Dial Transplant,2002,17(8):1480-1486.
[74]Stompor T, Zdzienicka A, Motyka M, et al. Selected growth factors in peritoneal dialysis: Their relationship to markers of inflammation, dialysis adequacy, residual renal function, and peritoneal membrane transport [J]. Perit Dial Int,2002,22(6):670-676.
[75]van Esch S, Zweers MM, Jansen MA, et al. Determinants of peritoneal solute transport rates in newly started nondiabetic peritoneal dialysis patients [J].Perit Dial Int,2004, 24(6):554-561.
[76]Szeto CC, Wong TY, Chow KM, et al. Dialysis adequacy and transport test for characterization of peritoneal transport type in Chinese peritoneal dialysis patients receiving three daily exchanges [J]. Am J Kidney Dis,2002,39(6):1287-1299.
[77]Zweers MM,Struijk DQSmit W,et al.Vascular endothelial growth factor in peritoneal dialysis:a longitudinal follow-up [J]. J Lab Clin Med,2001,137(2):125-132.
[78]张苗,蒋春明,孙净.黄芪对腹膜透析相关腹膜间皮细胞VEGF分泌和表达的影响[J].医 学临床研究,2005,22,(12)：1647-1650.
[79]Rodrigues A, Martins M, Santos MJ, et al.Evaluation of effluent markers cancer antigen 125, vascular endothelial growth factor, and interleukin-6:Relationship with peritoneal transport [J]. Adv Perit Dial,2004,20:8-12.
[80]Mandl-Weber S, Cohen CD, Haslinger B, et al. Vascular endothelial growth factor production and regulation in human peritoneal mesothelial cells [J]. Kidney Int,2002, 61(2):570-578.
[81]Szeto CC, Chow KM, Wong TY, et al.Feasibility of resuming peritoneal dialysis after severe peritonitis and Tenckhoff catheter removal [J]. J Am Soc Nephrol,2002,13(4): 1040-1045.
[82]De Vriese AS, Mortier S, Lameire NH. What happens to the peritoneal membrane in long-term peritoneal dialysis [J]. Perit Dial Int,2001,21 [Suppl 3]:S9-S18.
[83]Seo MJ, Oh SJ, Kim SI, et al. High glucose dialysis solutions increase synthesis of vascular endothelial growth factors by peritoneal vascular endothelial cells [J]. Perit Dial Int, 2001,21 Suppl 3:S35-40.
[84]Park SH, Lee EG, Kim IS, et al. Effect of glucose degradation products on the peritoneal membrane in a chronic inflammatory infusion model of peritoneal dialysis in the rat [J]. Perit Dial Int,2004,24(2):115-122.
[85]Eyries M, Collins T, Khachigian LM, et al. Modulation of growth factor gene expression in vascular cells by oxidative stress [J]. Endothelium,2004,11(2):133-139.
[86]Nilsson-ThorelⅠ CB, Muscalu N, Andren AH, et al.Heat sterilization of fluids for peritoneal dialysis gives rise to aldehydes [J]. Petit Dial Int,1993,13(3):208-213.
[87]Godbout JP, Pesavento J, Hartman ME, et al. Methylglyoxal enhances Cisplatin-indueed eytotoxicity by activating protein kinase Cdelta [J]. J Biol Chem,2002,277(4):2554-2561.
[88]Fan X, Subramaniam R, Weiss MF, et al. Methylglyoxal-bovine serum albumin stimulates tumor necrosis factor alpha secretion in RAW 264.7 cells through activation of mitogen-activating protein kinase, nuclear factor kappaB and intracell-ular reactive oxygen species formation [J]. Arch Biochem Biophys,2003,409(2):274-286.
[89]Ward RA, McLeish KR. Methylglyoxal:a stimulus to neutrophil oxygen radical production in chronic renal failure [J]. Nephrol Dial Transplant,2004,19(7):1702-1707.
[90]Aroeira LS, Aguilera A, Selgas R, et al. Mesenchymal conversion of mesothelial cells as a mechanism responsible for high solute transport rate in peritoneal dialysis:role of vascular endothelial growth factor [J]. Am J Kidney Dis,2005,46(5):938-948.
[91]Aquilera A, Aroeira LS, Ramirez-Huesca M, et al. Effects of rapamycin on the epithelial-to-mesenchymal transition of human peritoneal mesothelial cells [J]. Int J Artif Organs,2005,28(2):164-9.
[92]Mamputu JC, Renier G. Advanced glycation end products increase,through a protein kinase C dependent pathway,vascular endothelial growth factor expression in retinal endothelial cells.Inhibitory effect of gliclazide [J]. J Diabetes Complications,2002,16(4):284-293.
[93]Gunal AI, Celiker H, Akpolat N, et al.By reducing production of vascular endothelial growth factor octreotide improves the peritoneal vascular alterations induced by hypertonic peritoneal dialysis solution [J]. Petit Dial Int,2002,22(3):301-306.
[94]Zweers MM, de Waart DR, Smit W, et al. Growth factors VEGF and TGF-beta1 in peritoneal dialysis [J]. J Lab Clin Med,1999,134(2):124-132.
[95]Pawlaczyk K, Polubinska A, Numata N, et al. Vascular endothelial growth factor in dialysate in relation to intensity of peritoneal inflammation [J]. Int J Artif Organs,2008, 31(6):535-544.
[96]Leung JC, Chan LY, Tam KY, et al. Regulation of CCN2/CTGF and related cytokines in cultured peritoneal cells under conditions simulating peritoneal dialysis [J]. Nephrol Dial Transplant,2009,24(2):458-469.
[97]Pecoits-Filho R, Araujo MR, Lindholm B, et al. Plasma and dialysate IL-6 and VEGF concentrations are associated with high peritoneal solute transport rate [J]. Nephrol Dial Transplant,2002,17(8):1480-1486.
[98]Eckenstein FP. Fibroblast growth factors in the nervous system [J]. J Neurobiol,1994,25 (11):467-480.
[99]Muthukrishnan L,Warder E,Mcneil PL. Basic fibroblast growth factor is efficiently released from a cytolsolic storage site through plasma membrane disruption of endothelial cells [J]. J Cell Physiol,1991,148:1.
[100]Patsone G, Pasquale EB,Maher PA. Different mambrane of the fibroblast growth factor receptor family are specific to distinct cell types in the developing chicken embryo [J]. Dev Biol,1993,155:107.
[101]Philips GD, Schilb LA, Fiegel VD, et al. Angiogenic extract from skeletal muscle stimulates monocyte and endothelial cell chemotaxis in vitro [J]. Proc Soc Exp Biol Med, 1991,197:458.
[102]Marcus VC, Sylvis S, Helmut K, et al. Basic fibroblast growth factor synthesis by human peritoneal mesothelial cells induction by interleukin-1[J]. Am J Path,1999,155(6):1977-1984.
[103]刘映红,袁芳,肖平,等TGF-p1对人腹膜间皮细胞分泌细胞外基质和bFGF的影响[J].中国现代医学杂志,2002,12(14)：10-13.
[104]Chavakis T, Bierhaus A, Nawroth PP, et al. RAGE(receptor for advanced glycation end products):a central player in the inflammatory response [J]. Microbes Infect, 2004,6:1219-1225.
[105]陆福明,顾亢霞,郭晓敏等.终末期糖基化产物在尿毒症患者血清中的水平及血管壁和腹膜上的表达[J].中华肾脏病杂志,2000,16：147-151.
[106]Thornalley PJ. Advanced glycation end products in renal failure [J]. J Ren Nutr,2006,16: 178-184.
[107]Honda K, Nitta K, Horita S, et al. Accumulation of advanced glycation end products in the peritoneal vasculature of continuous ambulatory peritoneal dialysis patients with low ultrafiltration [J].Nephrol Dial Transplant,1999,14:1541-1549.
[108]Nakarnura S, Niwa T. Advaneed glycation end-products and peritoneal sclero-sis [J]. Semin Nephrol,2004,24(5):502-505.
[109]Nakayama M, Yoshimura K, Maruyama Y, et al. Possible involvement of cross-linking advanced glycation end products in long-term CAPD peritoneal degeneration [J]. Nephrol Dial Transplant,2004,19(6):1664-1665.
[110]De Vriese AS, Tilton RQ Mortier S, et al. Myofibroblast transdifferentiation of mesothelial cells is mediated by RAGE and contributes to peritoneal fibrosis in uraemia [J]. Nephrol Dial Trans Plant,2006,21(9):2549-2555.
[111]Boulanger E, Wautier MP, Gane P, et al.The triggering of human peritoneal mesothelial cell apoptosis and oncosis by glucose and glycoxydation products [J]. Nephrol Dial Transplant, 2004,19(9):2208-2216.
[112]Higuchi C, Nishimura H, Sanaka T. Biocompatibility of peritoneal dialysis fluid and influence of compositions on peritoneal fibrosis [J]. Ther Apher Dial,2006,10(4):372-379.
[113]DeYriese AS, Flyvbjerg A, Mortier S, et al. Inhibition of the interaction of AGE-RAGE prevents hyperglycemia-induced fibrosis of the peritoneal membrane [J]. J Am Soc Nephrol,2003,14(8):2109-2118.
[114]Schwenger V, Morath C,Salava A,et al. Damage to the peritoneal membrane by Glucose degradation produets is mediated by the receptor for advanced glycation end produets [J]. J Am Soc NePhrol,2006,17(1):199-207.
[115]Demir AY, Groothuis PG, Nap AW, et al. Menstrual effluent induces epithelial-mesenchymal transitions in mesothelial cells [J]. Hum Reprod,2004,19(1):21-29
[116]Ogata S, Yorioka N, Kohno N. Glucose and prednisolone alter basic fibroblast growth factor expression in peritoneal mesothelial cells and fibroblasts [J]. J Am Soc Nephrol, 2001,12(12):2787-2796.
[117]Ogata S, Naito T, Yorioka N, et al. Effect of lactate and bicarbonate on human peritoneal mesothelial cells, fibroblasts and vascular endothelial cells, and the role of basic fibroblast growth factor [J]. Nephrol Dial Transplant,2004,19(11):2831-2837.
[118]O'Reilly MS, Boehm T, Folkman J, et al. Endostatin:an endogenous inhibitor of angiogenesis and tumor growth [J]. Cell,1997,88(2):277-285.
[119]Hohenester E, Sasaki T, Olsen BR, et al.Crystal structure of the angiogenesis inhibitor endostatin at 1.5 A resolution [J]. EMBO J,1998;17(6):1656-1664.
[120]Standker L, Enger A, Schulz-Knappe P, et al.Structural and functional charac-terization of vitronectin-derived RGD-containing peptides from human hemofiltrate [J]. Eur Biochem, 1996,241:557-563.
[121]Dhanabal M, Ramchandran R, Volk R, et al.Endostatin:yeast production, mutants, and antitumor effect in renal cell carcinoma [J]. Cancer Res,1999,59(1):189-197.
[122]Ergun S, Kilic N, Wurmbach JH, et al.Endostatin inhibits angiogenesis by stabilization of newly formed endothelial tubes [J]. Angiogenesis,2001,4:193-206.
[123]Shichiri M, Hirata Y. Antiangiogenesis signals by endostatin [J]. FASEB J,2001,15: 1044-1053
[124]Yin G, Liu W, An P, et al. Endostatin gene transfer inhibits joint angiogenesis and pannus formation in inflammatory arthritis [J]. Mol Ther,2002,5(5 Pt 1):547-554.
[125]Berger AC, Feldman AL, Gnant MF, et al.The angiogenesis inhibitor, endostatin, does not affect murine cutaneous wound healing [J].J Surg Res,2000,91(1):26-31.
[126]Hanai J, Dhanabal M, Karumanchi SA, et al. Endostatin causes G1 arrest of endothelial cells through inhibition of cyclin D1 [J]. J Biol Chem,2002,277(19):16464-16469.
[127]Dhanabal M,Ramchandran R,Waterman MJ, et al. Endostatin induces endothelial cell apoptosis [J]. J Biol Chem,1999,274(17):11721-11726.
[128]Kim YM, Jang JW, Lee OH, et al. Endostatin inhibits endothelial and tumor cellular invasion by blocking the activation and catalytic activity of matrix metalloproteinase [J]. Cancer Res,2000,60(19):5410-5413.
[129]Macdonald N J, Shivers WY, Narum DL, et al. Endostatin binds tropomyosin. A potential modulator of the antitumor activity of endostatin [J]. J Biol Chem,2001,276(27): 25190-25196.
[130]Rehn M, Veikkola T, Kukk-Valdre E, et al. Interaction of endostatin with integrins implicated in angiogenesis [J]. Proc Natl Acad Sci USA,2001,98(3):1024-1029.
[131]Kim YM, Hwang S, Kim YM, et al. Endostatin blocks vascular endothelial growth factor-mediated signaling via direct interaction with KDR/Flk-1[J]. J Biol Chem,2002, 277(31):27872-27879.
[132]Walgenbach KJ, Gorospe JR, Gratas CA. Potential role for mast cells in the release of bFGF from normal myocytes during angiogenesis in vivo [J]. J Invest Surg 2002, 15(3):153.
[133]Nissen NN, Polverini PJ, Koch AE, et al. Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing [J]. Am J Pathol,1998, 152(6):1445-1452.
[134]Ryuto M, Ono M, Izumi H. Induction of vascular endothelial growth factor by tumor necrosis factor alpha in human glioma cells.possible roles of SP-1 [J]. J Bio Chem,1996, 271(45):28220.
[135]Pepper MS, Mandriota SJ, Vassalli JD, et al. Angiogenesis regulating cytokines:actions and interactions [J]. Curr Top Microbiol Immunol,1996,213:31.
[136]Funatsu H, Yamashita H, Noma H, et al. Stimulation and inhibition of angiogenesis in diabetic retinopathy [J]. Jpn J Ophthalmol,2001,45:577-584.
[137]Sasaki T, Larsson H, Kreuger J, et al. Structure basis and potential of heparin/hepatan sulfate binding to the angiogenesie inhibitor endostatin [J].Embo J,1999,18(22):6240-6248
[138]Ribatti D. The seminal work of Werner Risau in the study of the development of the vascular system [J]. Int J Dev Biol,2010,54(4):567-572.
[139]Przybylski M. A review of the current research on the role of bFGF and VEGF in angiogenesis [J]. J Wound Care,2009,18(12):516-519.
[140]Dai H, Zhao S, Xu L, et al. Expression of Efp, VEGF and bFGF in normal, hyperplastic and malignant endometrial tissue [J]. Oncol Rep,2010,23(3):795-799.
[2]Fischbach M, Haraldsson B, Helms P, et al. The peritoneal membrane:a dynamic dialysis membrane in children [J]. Adv Perit Dial,2003,19:265-268.
[3]Szeto CC, Chow KM, Kwan BC, et al. The relationship between bone morphogenic protein-7 and peritoneal transport characteristics [J]. Nephrol Dial Transplant,2008, 23:2989-2994.
[4]Mujais S, Krediet R, Lindholm B, et al. Evaluation and management of ultra filtration problems in peritoneal dialysis. International Society for peritoneal Dialysis Ad Hoc Committee on Ultra filtration Management In Peritoneal Dialysis [J]. Perit Dial Int,2000, 20[Suppl4]:S5-21.
[5]Heimburger O, Waniewski J, Werynski A, et al. Peritoneal transport in CAPD Patients with Permanent loss of ultra filtration capacity [J]. Kidney int,1990,38:495-506.
[6]Smit W, Langedijk MJ, Schouten N, et al. A comparison between 1.36% and 3.86% glucose dialysis solution for the assessment of peritoneal membrane function [J]. Perit Dial Int, 2000,20:734,741.
[7]Williams JD, Craig KJ, Top ley N, et al. Morphologic changes in the peritoneal membrane of patients with renal disease [J]. J Am Soc Nephrol,2002,13:470-479.
[8]Margetts PJ, Gyorffy S, Kolb M, et al. Antiangiogenic and antifibroticgene therapy in a chronic infusion model of peritoneal dialysis in rats [J]. J Am Soc Nephrol,2002,13: 721-728.
[9]Honda K, Nitta K, Hofita S, et al. Accumulation of advanced glyeation end product sin the peritoneal vasculature of continuous ambulatory peritoneal dialysis patients with low ultra-filtration [J]. Nephrol Dial Transplant,1999,14(6):1541-1549.
[10]Mateijsen MA, van der Wal AC, Hendriks PM, et al. Vascular and interstitial changes in the peritoneum of CAPD patients with peritoneal sclerosis [J]. Perit Dial Int,1999,19(6): 517-525.
[11]De Vriese AS, Mortier S, Lameire NH. What happens to the peritoneal membrane in long-term peritoneal dialysis [J].Perit Dial Int,2001,21 [Suppl 3]:S9-S18.
[12]Vardhan A, Zweers MM, Gokal R, et al. A solutions portfolio approach in peritoneal dialysis [J]. Kidney Int,2003,64 [Suppl88]:S114-S123.
[13]De Vriese AS, Tilton RG, Stephan CC, et al. Vascular endothelial growth factor is essential for hyperglycemia-induced structural and functional alterations of the peritoneal membrane [J]. JAm Soc Nephrol,2001,12:1734-1741.
[14]Fabbrini P, Zareie M, ter Wee PM, et al. Peritoneal exposure model in the rat as a tool to unravel bio(in)compatibility of PDF [J]. Nephrol Dial Transplant,2006,21[Suppl 2]:8-11.
[15]Kim YL, Do J, Park SH, et al. Low glucose degradation products dialysis solution modulates the levels of surrogate markers of peritoneal inflammation, integrity, and angiogenesis:Preliminary report [J]. Nephrology (Carlton),2003,8 Suppl:S28-32.
[16]Nakamura S, Tachikawa T, Tobita K, et al. Role of advanced glycation end products and growth factors in peritoneal dysfunction [J]. Am J KidneyDis,2003,41 [Suppll]:S61-S67.
[17]Zareie M, De Vriese AS, Hekking LH, et al. Immunopathological changes in a uremic rat model for peritoneal dialysis [J]. Nephrol Dial Transp lant,2005,20:1350-1361
[18]Thornalley PJ. Advanced glycation end products in renal failure [J]. J Ren Nutr,2006,16: 178-184.
[19]Mohammad Zareiel, An S. De Vriese, Liesbeth H. P, et al. Immunopathological changes in a uremic rat model for peritoneal dialysis [J]. Nephrol Dial Transplant,2005,20:1350-136.
[20]Mujais S, Nolph K, Gokal R, et al. Evaluation and management of ultra filtration problems in peritoneal dialysis. International Society for Peritoneal Dialysis Ad Hoc Committee on Ultra filtration Management in Peritoneal Dialysis [J]. Perit Dial Int,2000,20(supple 4):S5-S21.
[21]Toi M, Matsumoto T, Bnado H. Vascular endothelial growth factor:its prognostic, predictive and therapeutic implications [J]. Lancet Oncol,2001,2:667-673.
[22]Combet S, Miyata I, Moulin P, et al. Vascular proliferation and enhanced expression of endothelial nitric oxide synthase in human perioneum exposed to long-term periotneal dialysis [J]. J Am Soc Nephrol.2000.11:717-728.
[23]Szeto CC, Chow KM, Wong TY, et al. Feasibility of resuming peritoneal dialysis after severe peritonitis and Tenchhoff catheter removal [J]. J Am Soc Nephrol 2002; 13:1040-5.
[24]Murakami M, Simons M. Fibroblast growth factor regulation of neovascularization [J]. Curr Opin Hematol.2008,15:215-220.
[25]Yan W, Bentley B, Shao R. Distinct Angiogenic Mediators are Required for bFGF and VEGF-induced Angiogenesis:the Role of Cytoplasmic Tyrosine Kinase c-Abl in Tumor Angiogenesis [J]. Mol Biol Cell,2008, May; 19:2278-2288.
[26]Horiguchi H, Jin L, Ruebel KH, et al. Regulation of VEGF-A,VEGFR-I, thrombospondin-1,-2, and-3 expression in a human pituitary cell line (HP75) by TGFbetal, bFGF, and EGF [J]. Endocrine,2004,24:141-146.
[27]Marcus VC, Sylvis S, Helmut K, et al. Basic fibroblast growth factor synthesis by human peritoneal mesothelial cells induction by interleukin-1 [J]. Am J Path,1999,155:1977-1984.
[28]O'Reilly MS, Boehm T, Shing Y, et al. Endostatin:An Endogenous inhibitor of angiogenesis and tumor growth [J]. Cell,1997,88:277-285.
[29]Wenzel D, Schmidt A, Riemann K, et al. Endostatin, the proteolytic fragment of collagen ⅩⅧ, induces vasorelaxation [J]. Cir-cul Res,2006,98:1203-1211.
[30]Rehn M, Veikola T, kukk-Valdre, et al. Interactin of endostatin with integrins implicated in angiogenesis [J]. Cell Biology,2001,98:1024-1029.
[31]Kim YM, Hwang S, Kim YM, et al. Endostatin blocks vascular endothelial growth factor-mediated signaling via direct interaction with KDR/Flk-1[J]. J Biol Chem,2002, 277(31):27872-27879.
[32]张晓东,钱家麒.一种简便的正常大鼠腹膜透析模型建立[J].中国血液净化,2005,4：326-328.
[33]Jimi T, Wakayama Y, Inouc M, et al. Aquporin 1:Examination of its expression and localization in normal human skeletal muscle tissue [J]. Cells Tissues Organ, 2006,184:181-187.
[34]Chadban SJ, Briganti EM, Kerr PG, et al. Prevalence of kidney damage in Australian adults: the Aus Diab Kidney Study [J]. J Am Soc Nephrol,2003,14:S131-S138.
[35]ShahabI, Khanna R, Nolph KD. Peritoneal dialysis or hemodialysis? A dilemma for the nephrologist [J]. Adv Perit Dial,2006,22:180-5.
[36]Nagy J. Peritoneal dialysis thrapy [J]. Kidney Int,1997:62(suppl):S105-7.
[37]Zweers MM, Splint LJ, Krediet RT, Struijk DG, et al. Ultrastructure of basement membranes of peritoneal capillaries in a chronic peritoneal infusion model in the rat [J]. Nephrol Dial Transplant,2001,16:651-4.
[38]De Vriese AS, Tilton RG, Stephan CC, et al. Vascular endothelial growth factor is essential for hyperglycemia-induced structural and functional alterations of the peritoneal membrane [J]. J Am Soc Nephrol,2001,12:1734-41.
[39]Zeltzer E, Klein O, Rashid G, et al. Intraperitoneal infusion of glucose-based dialysate in the rat--an animal model for the study of peritoneal advanced glycation end-products formation and effect on peritoneal transport [J]. Perit Dial Int,2000,20:656-61.
[40]Boulanger E, Grossin N, Wautier MP, et al. Mesothelial RAGE activation by AGEs enhances VEGF release and potentiates capillary tube formation [J]. Kidney Int,2007; 71(2):126-33.
[41]于青,赵东杰,姚建等.高糖、尿毒症血清对人腹膜间皮细胞VEGF表达的影响[J].中国血液净化,2005,7：379-392.
[42]Aquilera A, Aroeira LS, Ramirez-Huesca M, et al. Effects of rapamycin on the epithelial-to-mesenchymal transition of human peritoneal mesothelial cells [J]. Int J Artif Organs. 2005,28(2):164-9.
[43]Aroeira LS, Aquilera A, Selgas R, et al. Mesenchymal conversion of mesothelial cells as a mechanism responsible for high solute transport rate in peritoneal dialysis:role of vascular endothelial growth factor [J]. Am J Kidney Dis.2005,46(5):938-48.
[44]郭群英,李晓艳,余学清等.腹膜透析液诱导结缔组织生长因子在大鼠腹膜间皮细胞表达[J].中华肾脏病杂志,2006,22(2)：114-118.
[45]陆福明,顾亢霞,郭晓敏等.终末期糖基化产物在尿毒症患者血清中的水平及血管壁和腹膜上的表达[J].中华肾脏病杂志,2000,16：147-151.
[46]Honda K, Hamada C, Nakayama M, et al. Impact of uremia, diabetes, and peritoneal dialysis itself on the pathogenesis of peritoneal sclerosis:a quantitative study of peritoneal membrane morphology [J]. Clin J Am Soc Nephrol,2008,3:720-8.
[47]Nakayama M, Yoshimura K, Maruyama Y, et al. Possible involvement of cross-linking advanced glycation endproducts in long-term CAPD peritoneal degeneration [J]. Nephrol Dial Transplant,2004,19:1664-1665.
[48]Chin D, Boyle GM, Parsons PG, et al. What is transforming growth factor-beta (TGF-beta) [J]. Br J Plast Surg,2004,57:215-221.
[49]Groppe J, Hinck CS, Samavarchi-Tehrani P, et al. Cooperative assembly of TGF-beta superfamily signaling complexes is mediated by two disparate mechanisms and distinct modes of receptor binding [J]. Mol Cell,2008,29:157-168.
[50]Wu XL, Zeng WZ, Jiang MD, et al. Effect of Oxymatrine on the TGF beta-Smad signaling pathway in rats with CCl(4)-induced hepatic fibrosis [J]. World J Gastroenterol,2008,14: 2100-2105.
[51]Selgas R, Bajo A. Epithelial-to-mesenchymal transition of mesothelial cell-its role in the response of the peritoneum to dialysis [J]. Nephrol Dial Transplant,2006,21:112-117.
[52]Tanabe K, Maeshima Y, Ichinose K, et al. Endostatin peptide, an inhibitor of angiogenesis, prevents the progression of peritoneal sclerosis in a mouse experimental model [J]. Kidney Int,2007,71:227-238.
[53]刘凡,王小宜,刘运生等.垂体腺瘤VEGF、bFGF和内皮抑素：mRNA表达与血管生成的关系[J].医学临床研究,2006,23：1172-1174.
[54]Heimburger O, Wang T, Lindholm B. Alterations in water and solute transport with time on peritoneal dialysis [J]. Perit Dial Int 1999; 19(2):S83-S90.
[55]Hohenester E, Sasaki T, Olsen BR, et al. Crystal structure of the angiogenesis inhibitor endostatin at 1.5A resolution [J]. Embo J,1998,17:1656-1664.
[56]Gaetzner S, Deckers MM, Stahl S, et al. Endostatin's heparin sulfate-binding site is essential for inhibition of angiogenesis and enhances in situ binding to capillary-like structure in bone explants [J]. Matrix Biol,2005,23:557-561.
[57]Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis [J]. Cell,1996,86:353-364.
[58]Io H, Hamada C, Ro Y, et al. Morphologic changes of peritoneum and expression of VEGF in encapsulated peritoneal sclerosis rat models [J]. Kidney Int,2004,65:1927-1936.
[1]El Nahas AM, Belb AK. Chronic Kidney disease:the global challenge [J]. Lancet, 2005,365:331-340.
[2]Lysaght MJ. Maintenance dialysis population dynamics current trends and long-term implications [J]. JAM Soc Nephrol,2002,13:37-40.
[3]王海燕.译后评论：我国慢性肾脏病的新数据及其警示[J].英国医学杂志(中文版),2006,9(3)：136.
[4]Mujais S, Nolph K, Gokal R, et al. Evaluation and management of ultrafiltration problems in peritoneal dialysis. International Society for Peritoneal Dialysis Ad Hoc Committee on Ultrafiltration Management in Peritoneal Dialysis [J]. Perit Dial Int,2000,20(supple 4):S5-S21.
[5]Toi M, Matsumoto T, Bnado H. Vascular endothelial growth factor:its prognostic, predictive and therapeutic implications [J]. Lancet Oncol,2001,2:667-673.
[6]Combet S, Miyata I, Moulin P, et al. Vascular proliferation and enhanced expression of endothelial nitric oxide synthase in human perioneum exposed to long-term periotneal dialysis [J]. J Am Soc Nephrol,2000,11:717-728.
[7]Szeto CC, Chow KM, Wong TY, et al. Feasibility of resuming peritoneal dialysis after severe peritonitis and Tenchhoff catheter removal [J]. J Am Soc Nephrol 2002; 13:1040-5.
[8]Murakami M, Simons M. Fibroblast growth factor regulation of neovascularization [J]. Curr Opin Hematol,2008,15:215-20.
[9]Yan W, Bentley B, Shao R. Distinct Angiogenic Mediators are Required for bFGF and VEGF-induced Angiogenesis:the Role of Cytoplasmic Tyrosine Kinase c-Abl in Tumor Angiogenesis [J]. Mol Biol Cell,2008, May; 19:2278-88.
[10]Horiguchi H, Jin L, Ruebel KH, et al. Regulation of VEGF-A,VEGFR-I, thrombospondin-1,-2, and -3 expression in a human pituitary cell line (HP75) by TGFbetal, bFGF, and EGF [J]. Endocrine,2004,24:141-146.
[11]Marcus VC, Sylvis S, Helmut K, et al. Basic fibroblast growth factor synthesis by human peritoneal mesothelial cells induction by interleukin-1 [J]. Am J Path,1999,155:1977-1984.
[12]O'Reilly MS, Boehm T, Shing Y, et al. Endostatin:An Endogenous inhibitor of angiogenesis and tumor growth [J]. Cell,1997,88:277-285.
[13]Wenzel D, Schmidt A, Riemann K, et al. Endostatin, the proteo-lytic fragment of collagen XVIII, induces vasorelaxation [J]. Cir-cul Res,2006,98:1203-1211.
[14]Rehn M, Veikola T, kukk-Valdre, et al. Interactin of endostatin with integrins implicated in angiogenesis [J]. Cell Biology,2001,98:1024-1029.
[15]Nagy J. Peritoneal dialysis thrapy[J]. Kidney Int,1997:62(suppl):S105-7.
[16]Smit W, Schouten N, van den Berg N, et al. Analysis of the prevalence and causes of ultrafiltration failure during long-term peritoneal dialysis:a cross-sectional study [J]. Perit Dial Int,2004,24:506-508.
[17]Chadban SJ, Briganti EM, Kerr PG, et al. Prevalence of kidney damage in Australian adults: the Aus Diab Kidney Study [J]. J Am Soc Nephrol,2003,14:S131-S138.
[18]ShahabI, Khanna R, Nolph KD. Peritoneal dialysis or hemodialysis? A dilemma for the nephrologist [J]. Adv Perit Dial,2006,22:180-5.
[19]Zareie M, Fabbrini P, Hekking LH, et al. Novel role for mastcells in omental tissue remodeling and cell recruitment in experimental peritoneal dialysis [J]. J Am Soc Nephrol, 2006,17:3447-3457.
[20]赵占正,刘章锁,李艳等.内皮抑素在大鼠腹膜的表达及其与腹膜血管新生的关系[J],中华肾脏病杂志,2009,6：437-440.
[21]Boulanger E, Grossin N, Wautier MP, et al. Mesothelial RAGE activation by AGEs enhances VEGF release and potentiates capillary tube formation [J]. Kidney Int,2007,71: 126-133.
[22]Combet S, Miyata I, Moulin P, et al. Vascular proliferation and enhanced expression of endothelial nitric oxide synthase in human perioneum exposed to long-term periotneal dialysis [J]. J Am Soc Nephrol,2000.11:717-728.
[23]Szeto CC, Chow KM, Wong TY, et al. Feasibility of resuming peritoneal dialysis after severe peritonitis and Tenchhoff catheter removal [J]. J Am Soc Nephrol,2002; 13:1040-5.
[24]于青,赵东杰,姚建等.高糖、尿毒症血清对人腹膜间皮细胞VEGF表达的影响[J].中国血液净化,2005,7：379-392.
[25]Aquilera A, Aroeira LS, Ramirez-Huesca M, et al. Effects of rapamycin on the epithelial-to-mesenchymal transition of human peritoneal mesothelial cells [J]. Int J Artif Organs, 2005;28(2):164-9.
[26]Aroeira LS, Aquilera A, Selgas R, et al. Mesenchymal conversion of mesothelial cells as a mechanism responsible for high solute transport rate in peritoneal dialysis:role of vascular endothelial growth factor [J]. Am J Kidney Dis,2005;46(5):938-48.
[27]郭群英,李晓艳,余学清等.腹膜透析液诱导结缔组织生长因子在大鼠腹膜间皮细胞表达[J].中华肾脏病杂志,2006,22(2)：114-118.
[28]Murakami M, Simons M. Fibroblast growth factor regulation of neovascularization [J]. Curr Opin Hematol,2008,15:215-20.
[29]Yan W, Bentley B, Shao R. Distinct Angiogenic Mediators are Required for bFGF and VEGF-induced Angiogenesis:the Role of Cytoplasmic Tyrosine Kinase c-Abl in Tumor Angiogenesis [J]. Mol Biol Cell,2008, May; 19:2278-88.
[30]陆福明,顾亢霞,郭晓敏等.终末期糖基化产物在尿毒症患者血清中的水平及血管壁和腹膜上的表达[J].中华肾脏病杂志,2000,16：147-151.
[31]Nakayama M, Yoshimura K, Maruyama Y,et al. Possible involvement of cross-linking advanced glycation endproducts in long-term CAPD peritoneal degeneration [J]. Nephrol Dial Transplant,2004,19:1664-1665.
[32]Chin D, Boyle GM, Parsons PG, et al. What is transforming growth factor-beta (TGF-beta)? [J]. Br J Plast Surg,2004,57:215-21.
[33]Selgas R, Bajo A, et al. Epithelial-to-mesenchymal transition of mesothelial cell—its role in the response of the peritoneum to dialysis [J]. Nephrol Dial Transplant,2006,21:112-7.
[34]Wenzel D, Schmidt A, Riemann K, et al. Endostatin, the proteo-lytic fragment of collagen XVIII, induces vasorelaxation [J]. Cir-cul Res,2006,98:1203-1211.
[35]Kim YM, Hwang S, Kim YM, et al. Endostatin blocks vascular endothelial growth factor-mediated signaling via direct interaction with KDR/Flk-1[J]. J Biol Chem,2002, 277(31):27872-27879.
[36]Tanabe K, Maeshima Y, Ichinose K, et al. Endostatin peptide, an inhibitor of angiogenesis, prevents the progression of peritoneal sclerosis in a mouse experimental model [J]. Kidney Int,2007,71:227-238.
[37]刘凡,王小宜,刘运生等.垂体腺瘤VEGF、bFGF和内皮抑素nRNA表达与血管生成的关系[J].医学临床研究,2006,23：1172-1174.
[38]Aroeira LS, Aguilera A, Selgas R, et al. Mesenchymal conversion of mesothelial Cells as a mechanism responsible for high solute transport rate inperitonealdialysis:role of vascular endothelial growth factor [J]. Am J Kidney Dis,2005,46(5):938-948.
[39]Walgenbach KJ, Gorospe JR, Gratas C. A potential role for mast cells in the release of bFGF from normal myocytes during angiogenesis in vivo [J]. Journal of investigative surgery,2002,15(3):153.
[40]Nissen N N, Polverini P J, Koch A E, et al. Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing [J]. Am J Pathol,1998, 152(6):1445-1452.
[41]Ryuto M, Ono M, Izumi H, et al. Induction of vascular endothelial growth factor by tumor necrosis factor alpha in human glioma cells [J]. Possible roles of SP-1 1996,271(45):28220.
[42]Pepper MS, Mandriota SJ, Vassalli JD, et al. Angiogenesis regulating cytokines:actions and interactions [J]. Curr Top Microbiol Immunol,1996,213:31.
[43]Sasaki T, Larsson H, Kreuger J, et al. Stmcture basis and potential of heparin/hepatan sulfate binding to the angiogenesie inhibitor endostatin [J]. Embo J,1999,18(22): 6240-6248.
[44]Rehn M, Veikola T, kukk-Valdre, et al. Interactin of endostatin with integrins implicated in angiogenesis [J]. Cell Biology,2001,98:1024-1029.
[45]Hohenester E, Sasaki T, Olsen BR, et al. Crystal structure of the angiogenesis inhibitor endostatin at 1.5A resolution [J]. Embo J,1998,17:1656-1664.
[46]Gaetzner S, Deckers MM, Stahl S, et al. Endostatin's heparin sulfate-binding site is essential for inhibition of angiogenesis and enhances in situ binding to capillary-like structure in bone explants [J]. Matrix Biol,2005,23:557-561.
[47]Hanahan D, Folkman J. Patterns and emerging mechanisms of the an gio-genicseich during tumorigenesis [J]. Cell,1996,86(3):353-364.
[1]Yan W, Bentley B, Shao R. Distinct Angiogenic Mediators are Required for bFGF and VEGF-induced Angiogenesis:the Role of Cytoplasmic Tyrosine Kinase c-Abl in Tumor Angiogenesis [J]. Mol Biol Cell,2008,19(5):2278-2288.
[2]Horiguchi H, Jin L, Ruebel KH, et al. Regulation of VEGF,VEGFR-I, thrombospondin-1,-2, and-3 expression in a human pituitary cell line (HP75) by TGFbetal, bFGF, and EGF [J]. Endocrine,2004;24:141-146.
[3]Marcus VC,Sylvis S,Helmut K,et al.Basic fibroblast growth factor synthesis by human peritoneal mesothelial cells induction by interleukin-1 [J].Am J Path,1999,155:1977-1984.
[4]袁江姿,钱家麒,方炜等.尿毒症腹透对大鼠腹膜形态和功能的影响[J].上海交通大学学报(医学版),2007,27：1189-1192.
[5]Weidner N. Intratumor micro vessel density as prognostic factor in cancer [J]. Am J Pathol, 1995,147:9-11.
[6]Zareie M, De Vriese AS, Hekking LH, et al. Immunopathological changes in a uraemic rat model for peritoneal dialysis [J]. Nephrol Dial Transplant,2005; 20 (7):1350-1361.
[7]Ho-dac-Pannekeet MM, Atasever B, Struijk DG, et al. Analysis of ultrafiltration failure in peritoneal dialysis patients by means of standard peritoneal permeability analysis [J]. Perit Dial Int,1997; 17:144-150.
[8]Jorres A, Bender TO, Finn A et al. Biocompatibility and buffers:effect of bicarbonate-buffered peritoneal dialysis fluids on peritoneal cell function [J]. Kidney Int,1998;54(6): 2184-2193.
[9]Stigant CE, Bargman JM. What's new in peritoneal dialysis:biocompatibility and continuous flow peritoneal dialysis [J]. Curr Opin Nephrol Hypertens,2002; 11 (6):97-602.
[10]Lopez-Cabrera M, Aguilera A, Aroeira LS et al. Ex vivo analysis of dialysis effluent-derived mesothelial cells as an approach to unveiling the mechanism of peritoneal membrane failure [J]. Perit Dial Int,2006; 26(1):26-34.
[11]Combet S, Miyata T, Moulin P et al. Vascular proliferation and enhanced expression of endothelial nitric oxide synthase in human peritoneum exposed to long-term peritoneal dialysis [J]. J Am Soc Nephrol,2000; 11(4):717-728.
[12]Okada-Ban M, Thiery JP, Jouanneau J. Fibroblast growth factor-2 [J]. Int J Biochem Cell Biel,2000;32(3):263-267.
[13]Hohenester E, Sasaki T, Olsen BR, et al. Crystal structure of the angiogenesis inhibitor endostatin at 1.5A resolution [J]. Embo J,1998;17:1656-1664.
[14]Bellini MH, Coutinho EL, Filgueiras TC, et al. Endostatin expression in the murine model of ischaemia/reperfusion-induced acute renal failure [J]. Nephrology (Carlton),2007; 12: 459-465.
[15]Ai RZ, Wu Y, Liu Q, et al. Suppression of lung cancer in murine model:treated by combination of recombinant human endostsatin adenovirus with low-dose cisplatin [J]. Exp Clin Cancer Res,2009,5:28-31.
[16]Retsky MW, Hrushesky WJ, Gukas ID, et al. Hypothesis:primary antiangiogenic method proposed to treat early stage breast cancer [J]. BMC Cancer,2009, Jan 8; 9:7.
[17]汪涛,王英.腹膜透析的现状[J].医师进修杂志,2002,25(2)：13-15.
[18]Liem YS, Wong JB, Hunink MG, et al. Comparison of hemodialysis and peritoneal dialysis survival in the Netherlands [J]. Kidney Int,2007,71(2):153-158.
[19]Vonesh EF, Snyder JJ, Foley RN, et al. The differential impact of risk factors on mortality in hemodialysis and peritoneal dialysis [J]. Kidney Int,2004; 66 (6):2389-2401.
[20]Smit W, Schouten N, van den Berg N, et al. Analysis of the prevalence and causes of ultrafiltration failure during long-term peritoneal dialysis:a cross-sectional study [J]. Perit Dial Int,2004;24:506-508.
[21]Plum J, Hermann S, Fussholler A, et al. Peritoneal sclerosis in peritoneal dialysis patients related to dialysis settings and peritoneal transport properties [J]. Kidney Int,2001,78 Suppl:S42-7.
[22]Van Westrhenen R, Zweers MM, Kunne C, et al. A pyruvate-buffered dialysis fluid induces less peritoneal angiogenesis and fibrosis than a conventional solution [J]. Perit Dial Int, 2008; 28(5):487-96.
[23]Parikova A, Smit W, Struijk DG, et al. Analysis of fluid transport pathways and their determinants in peritoneal dialysis patients with ultrafiltration failure [J]. Kidney Int,2006; 70(11):1988-94.
[24]Hanahan D, Folkman J. Patterns and emerging mechanisms of the an-giogenic switch during tumorigenesis [J]. Cell,1996,86:353-364.
[25]Yoshio Y, Miyazaki M, Abe K, et al. TNP-470,an angiogenesis inhibitor, suppresses the progression of peritoneal fibrosis in mouse experimental model [J]. Kidney Int,2004; 66: 1677-1685.
[26]Senger DR, Galli SJ, Dvorak AM, et al. Tumor cells secrete a vascular permeability factor that promotes accumulation of ascites fluid [J]. Science,1983,219(4587):983-985.
[27]Leung DW, Cachianes G, Kuang WJ, et al. Vascular endothelial growth factor is a secreted angiogenic mitogen [J]. Science,1989;246:1306.
[28]Nowak DG, Woolard J, Amin EM, et al. Expression of pro-and anti-angiogenic isoforms of VEGF is differentially regulated by splicingand growth factors [J]. Cell Sci,2008,121: 3487-3495.
[29]awasaki T, Kitsukawa T, Bekku Y, et al. A requirement for neuropilin-1 in embryonic vessel formation [J]. Development,1999,126:4895-4902.
[30]Boulanger E, Grossin N, Wautier MP, et al. Mesothdial RAGE activation by AGEs enhances VEGF release and potentiates capillary tube formation [J]. Kidney Int,2007, 71(2):126-133.
[31]Combet S, Miyata T, Moulin P, et al. Vascular proliferation and enhanced expression of endothelial nitric oxide synthase in human peritoneum exposed to long-term peritoneal dialysis [J]. J Am Soc Nephrol,2000, 11(4):717-728.
[32]张晓东,钱家麒.一种简便的正常大鼠腹膜透析模型建立[J].中国血液净化,2005,4：326-328.
[33]O'Reilly MS, Boehm T, Folkman J, et al. Endostatin:an endogenous inhibitor of angiogenesis and tumor growth [J]. Cell,1997,88(2):277-285.
[34]Hohenester E, Sasaki T, Olsen BR, et al. Crystal structure of the angiogenesis inhibitor endostatin at 1.5 A resolution [J]. EMBO J,1998,17(6):656-1664.
[35]Folkman J. Antiangiogenesis in cancer therapy-endostatin and its mechanisms of action [J]. Exp. Cell Res,2006,3(12):594-607.
[36]柏树令,赵丹.CD34抗原的生物学特性及其临床应用[J].解剖科学进展,2005,11(1)：54-60.
[37]Abdollahi A, Hahnfeldt P, Maercker C, et al. Endostatin's antiangiogenic signaling network [J]. Mol. Cell,2004,13,649-663.
[38]Nyberg P, Xie L, Kalluri R. Endogenous inhibitors of angiogenesis [J]. Cancer Res,2005, 65,3967-3979.
[39]Kim Y M, Jang J W, Lee O H, et al. Endostatin inhibits endothelial and tumor cellular invasion by blocking the activation and catalytic activity of matrix metalloproteinase [J]. Cancer Res,2000,60(19):5410-5413.
[40]Rehn M, Veikkola T, Kukk-Valdre E, et al. Interaction of endostatin with integrins implicated in angiogenesis [J]. Proc Natl Acad Sci USA,2001,98(3):1024-1029.
[41]Kim Y M, Hwang S, Kim Y M, et al. Endostatin blocks vascular endothelial growth factor-mediated signaling via direct interaction with KDR/Flk-1 [J]. J Biol Chem,2002, 277(31):27872-27879.
[1]E1 Nahas AM, Belb AK. Chronic Kidney disease:the global challenge [J]. Lancet,2005; 365:331-340
[2]Lysaght MJ. Maintenance dialysis population dynamics current trends and long-term implications[J].J Am Soc Nephrol,2002;13:37-40
[3]Mato D, Alvarez-Aguilar C, Castaneda-Limones R, et al. Prevalence of chronic kidney disease in an urban Mexican population[J]. Kidney Int,2005;68(Suppl97); 11-17
[4]王海燕.译后评论：我国慢性肾脏病的新数据及其警示[J].英国医学杂志(中文版),2006；9(3)：136.
[5]Laucapis A, Keown P, Pus N, et al. A study of the quality of life and cost-utility of renal translation[J]. Kidney Int,1999;50:235-242.
[6]文吉秋,纪玉莲,郑智华,等.血液透析、腹膜透析和肾移植的成本-效果分析[J].中华肾脏病杂志,2005;21(10)：616-619
[7]Liem YS, Wong JB, Hunink MG, et al. Comparison of hemodialysis and peritoneal dialysis survival in the Netherlands [J]. Kidney Int,2007,71(2):153-158.
[8]Vonesh EF, Snyder JJ, Foley RN, et al. The differential impact of risk factors on mortality in hemodialysis and peritoneal dialysis [J]. Kidney Int,2004; 66(6):2389-2401.
[9]王峦,程晓明,张璐莹等.杭州市腹膜透析和血液透析治疗费用与疗效的比较研究[J].中国卫生资源,2009,12(3)：129-131.
[10]Musphy SW, Foley RN, Barrett BJ, et al. Comparative mortality of hemodialysis and peritoneal dialysis in Canada[J]. Kidney Int,2000,57:1720
[11]US Renal Data System, Exceptis from the USRDS 2000 Annual Data Re-port:Atlas of end-stage renal disease in the United States[J]. Am J Kidney Dis,2000; 36 (Suppl 2):S1
[12]Nagy J. Peritoneal dialysis therapy[J]. Kidney Int,1997:62(suppl):S105-7.
[13]Smit W, Schouten N, van den Berg N, et al. Analysis of the prevalence and causes of ultrafiltration failure during long-term perito-neal dialysis:a cross-sectional study[J]. Perit Dial Int,2004,24:506-508.
[14]Heimburger O, Wanjewski J,Werynski A,et al. Peritoneal transport in CAPD patients with permanent loss of ultrafltration capacity[J]. Kidney Int 1990,38:495-506.
[15]Ho-dac-Pannekeet MM, Atasever B, Struijk DG, et al.A nalysis of ultrafiitration failure in peritoneal dialysis patients by means of standard peritoneal permeability analysis[J]. Perit Dial Int,1997,17:144-150
[16]Mujais S, Nolph K, Gokal R, et al. Evaluation and management of ultrafiltration problems in peritoneal dialysis. International Society for Peritoneal Dialysis Ad Hoc Committee on Ultrafiltration Management in Peritoneal Dialysis[J]. Perit Dial Int,2000,20(supple 4):S5-S21.
[17]Williams JD, Craig KJ, Top ley N, et al. Morphologic changes in the peritoneal membrane of patients with renal disease[J]. J Am Soc Nephrol,2002,13:470-479.
[18]Mortier S, De Vriese As, Vanol, et al. Hemodynamic effects of peritoneal dialyse; solutions on the rat peritoneal membrane:Role of acidity, buffer choice, glucose concentration, and glucose degradation products[J]. J Am Soc Nephrol,2002,13:480-489
[19]Ates K, Koc R, Nergizoglu G, et al. The longitudinal effect of a single peritonitis episode on peritoneal membrane transport in CAPD patients[J]. Perit Dial Int,2000,20:220-226
[20]郭群英,李晓艳,余学清等.腹膜透析液诱导结缔组织生长因子在大鼠腹膜人腹膜间皮细胞AQP和FGF对腹膜超滤影响的实验研究间皮细胞表达[J].中华肾脏病杂志,2006,22(2)：114-118.
[21]于青,赵东杰,徐琦等.高糖、尿毒症血清对人腹膜间皮细胞VEGF表达的影响[J].中国血液净化,2005,4(7)：379-380.
[22]Davies SJ, Bryan J, Phillips L, et al. Longitudinal changes in peritoneal kinetics:The effects of peritoneal dialysis and peritonitis[J]. Nephrol Dial Transplant,1996,11:498-506.
[23]Zweers MM, Splint LJ, Krediet RT, et al. Ultrastructure of basement membranes of peritoneal capillaries in a chronic peritoneal infusion model in the rat [J]. Nephrol Dial Transplant,2001,16:651-654.
[24]Heimburger 0, Wang T, Lindholm B. Alterations in water and solute transport with time on peritoneal dialysis [J]. Perit Dial Int,1999,19 [Suppl 2]:583-590.
[25]Brownlee M. Biochemistry and molecular cell biology of diabetic complications [J]. Nature,2001;414:813-820
[26]De Vriese AS,Moritier S,Lameire NH.Glucotoxicity of the peritoneal membrane:the case for VEGF[J].Nephrol Dial Transplant,2001;16:2299-2302
[27]Zareie M, Keuning ED, ter Wee PM, et al. Improved biocompatibility of bicarbonate/ lactate-buffered PDF is not related to Ph[J]. Nephrol Dial Transplant,2006,21(1): 208-216.
[28]PENG Wei-sheng, ZHOU Qiao-ling, YU Xue-qing, et al. Effects and significance of different glucose concentrations and LPS on the expression of VEGF and vascular proliferation in the peritoneal membrane of dialysis rat [J]. China Journal of Modern Medicine,2007,17(17):2085-2088.
[29]Mateijsen MA, vander Wal AC, Hendriks PM, et al. Vascular and interstitial changes in the peritoneum of CAPD patients with peritoneal sclerosis [J]. Perit Dial Int,1999,19(6): 517-525.
[30]Tauer A, Knerr T, Niwa T, et al. In vitro formation of N(epsilon)-(carboxymethyl)-lysine and imidazolones under conditions similar to continuous ambulatory peritoneal dialysis [J]. Biochem Biophys Res Commun,2001;280:1408-1414.
[31]Witowski J, Wisniesska J, Korybalska D, et al. Prolonged exposure to glucose degradation products impairs viability and function of human peritoneal mesothelial cells [J]. J Am Noc Nephrol,2001,12:2434-2441.
[32]Inagi R, Miyata M, Yamamoto R, et al. Glucose degradation product methylglyoxal enhances the production of vascular endothelial growth factor in peritoneal cells:role in the functional and morphological alterations of peritoneal membranes in peritoneal dialysis [J]. FEBS Lett,1999;463(3):260-264.
[33]Davies SJ, Phillips L, Naish PF, et al. Peritoneal Glucose exposure and changes in membrane solute transport with time on peritoneal dialysis [J]. J Am Soc Nephrol,2001,12: 1046-1051.
[34]Selgas R, Bajo MA, Castro MJ, et al. Risk factors responsible for ultrafiltration failure in early stages of peritoneal dialysis [J]. Perit Dial Int,2000; 20:631-636.
[35]Sakamoto N, Sugimura K, Kawashima H, et al. Infulence of glucose and inflammatory eytokines on TGF-beta 1 and CTGF mRNA expression in human peritoneal mesothelial cells [J]. Int J Mol Med,2005,15(6):907-911.
[36]Rodrigues AS, Martins M, Korevaar JC, et al. Evaluation of peritoneal transport and membrane status in peritoneal dialysis:focus on incident fast transporters [J]. Am J Nephrol,2007,27:84-91.
[37]Reyes MJ, Bajo MA, Hevia C, et al. Inherent high peritoneal transport and ultrafiltration deficiency:their mid-term clinical relevance [J]. Nephrol Dial Transplant,2007,22:218-23.
[38]Lai KN, Lai KB, Lam CW, et al. Changes of cytokine profiles during peritonitis in patients on continuous ambulatory peritoneal dialysis [J]. Am J Kid Disease,2000,35:644-652.
[39]Combet S, Van Landschoot M, Moulin P, et al. Regulation of aquqporin-1 and nitric oxide synthase isoforms in a rat model of acute peritonitis [J]. J Am Soc Nephrol,1999,10: 2185-2196.
[40]Zareie M, De Vriese AS, Hekking LH, et al. Immunopathological changes in a uraemic rat model for peritoneal dialysis [J]. Nephrol Dial Transplant,2005,20(7):1350-1361.
[41]Miyata T, van Ypersele, de Strihou C, et al. Alterations in nonenzymatic biochemistry in uremia:origin and significance of carbonyl stress"in long-term uremic complications [J]. Kidney Int,1999,55(2):389-399.
[42]Kakuta T, Tanaka R, SatohY, et al. Pyridoxamine improves functional structural and biochemical alterations of peritoneal membranes in uremic peritoneal dialysis rats [J]. Kidney Int,2005,68(3):1326-1336.
[43]YUAN Jiang-z, QIAN Jia-qi, FANG Wei-sheng, et al. Morphologic and functional alterations of peritoneum in uremic rats undergoing peritoneal dialysis [J]. Journal of Shanghai Jiaotong University(Medical Science),2007,27 (10):1189-1992.
[44]Combet S, Ferrier ML, Van Landschoot M, et al.Chronic uremia induces permeability changes, increased nitric oxide synthase expression, and structural modifications in the peritoneum[J].J Am Soc Nephrol,2001;12:2146-2157
[45]Heaf JG, Sarac S, Afzal S. A high peritoneal large pore fluid flux causes hypoalbuminaemia and is a risk factor for death in peritoneal dialysis patients [J]. Nephrol Dial Transplant,2005,20:2194-2201
[46]Margetts PJ, Gyorffy S, Kolb M, et al. Antiangiogenic and antifibrotic gene therapy in a chronic infusion model of peritoneal dialysis in rats [J]. J Am Soc Nephrol,2002,13: 721-728.
[47]郭吴,李学军.细胞膜上的水通道--2003年诺贝尔化学奖工作介绍[J].生理科学进展,2007,38(3)：283.288.
[48]Lai KN, Li FK, Lan HY, et al. Expression of aquaporin-1 in human peritoneal mesothelial cells and its upregulation by glucose in vitro [J]. J Am Soc Nephrol,2001,12(5):1036-1045.
[49]方炜,钱家麒,余志远等.水孔蛋白-1在人腹膜组织的表达以及腹膜透析对其表达的影响[J].中华肾脏病杂志,2003,19(1)：29-33.
[50]Schoenicke G, Diamant R, Donner A, et al. Histochemical distribution and expression of aquaporin-1 in the peritoneum of patients undergoing peritoneal dialysis:Relation to peritoneal transport [J]. Am J Kidney Dis,2004,44(1):146-154.
[51]Ni J, Verbavatz JM, Rippe A, et al. Aquaporin 1 plays an essentiai role in water permeability and ultrafiltration during peritoneal dialysis [J]. Kidney Int,2006,69(9): 1518-1525.
[52]Goffin E, Combet S, Jamar F, et al. Expression of aquaporin-1 in a long-term peritoneale dialysis patient with impaired transcellular water transport [J]. Am J Kid Disease,1999, 33:383-388.
[53]Aroeira LS, Aguilera A, Sanchez Tomero JA, et al. Epithelial to mesenchymal transition and peritoneal membrane failure in peritoneal dialysis patients:pathologic significance and potential therapeutic interventions[J]. J Am Soc Nephrol,2007,18(7):2004-2013.
[54]Zarrinkalma KH, Stanley JM, Gray J, et al. Connectives tissue growth factor and its regulation in the peritoneal dialysis patitoneal diyalsis patients [J]. Kidney Int,2003, 64(1):331-338.
[55]Yao Q, Qian JQ, Lin XH, et al. Inhibition of the effect of high glucose on the expression of smad in human peritoneal mesothelial cells[J].Int J Artif Organs,2004,27:828-834.
[56]Mactier RA, Khanna R, Twardowski ZJ, et al. Ultrafiltration failure in continuous ambulatory peritoneal dialysis due to excessive peritoneal cavity lymphatic absorption [J]. Am J Kidney Dis,1987,10:461-466
[57]Flessner MF.Changes in the peritoneal interstitium and their effect on peritoneal transport [J]. Perit Dial Int,1999,19[Suppl 2]:77-82.
[58]刘宏富.长期腹膜透析超滤衰竭的预防及处理[J].中国中西医结合肾脏病杂志,2002,3：620-622.
[59]De Vriese AS, Tilton FG,Stephan CG.,et al..Diabetes induced microvascular proliferation and hypermeability in the peritoneum.role of vascular endothelial growth factor [J]. J Am Soc Nephrol,2001,12:1734-1741.
[60]Hanahan D, Folkman J. Patterns and emerging mechanisms of the an-giogenic switch during tumorigenesis [J]. Cell,1996,86:353-364.
[61]Tepper OM, Galiano RD, Kalka C, et al. Endothelial progenitor cells:the promise of vascular stem cells for plastic surgery [J]. Plast Reconstr Surg,2003,111:846.
[62]Bdolah Y, Sukhatme VP, Karumanchi SA.Angiogenic imbalance in the patho-physiology of preeclampsia:newer insights [J]. Semin Nephrol,2004;24:548-556.
[63]Senger DR, Galli SJ, Dvorak AM, et al. Tumor cells secrete a vascular per-meability factor that promotes accumulation of ascites fluid [J]. Science,1983; 219(4587):983-985.
[64]Leung DW, Cachianes G, Kuang WJ, et al. Vascular endothelial growth factor is a secreted angiogenic mitogen [J]. Science,1989,246:1306.
[65]Risau W. Mechanisms of angiongenesis [J]. Nature,1997,386(6626):671-674.
[66]Lei J, Jiang A, Pei D, et al. Identification and characterization of a new splicing variant of vascular endothelial growth factor:VEGF183 [J]. Biochim Biophys Acta,1998,1443 (3):400-406.
[67]Huang Z, Bao SD. Roles of main pro-and anti-angiogenic factors in tumor angiogenesis [J]. World J Gastroenterol,2004,10:463-470.
[68]Matsumoto C, Claesson WL. Sci-STKE,2001; 2001 (112):RE21.
[69]Eremina V, Sood M, Haigh J, et al. Glomerular-specific alterations of VEGF expression lead to distinct congenital and acquired renal diseases [J]. J Clin Invest,2003,111 (5):707-716.
[70]Ferrara N, Gerber HP, Le Couter J. The biology of VEGF and its receptors [J]. Nat Med,2003,9 (6):669-676.
[71]Boulanger E, Grossin N, Wautier MP, et al.Mesothdial RAGE activation by AGEs enhances VEGF release and potentiates capillary tube formation [J]. Kidney Int, 2007,71(2):126-133.
[72]Combet S, Miyata T, Moulin P, et al. Vascular proliferation and enhanced expression of endothelial nitric oxide synthase in human peritoneum exposed to long-term peritoneal dialysis [J]. J Am Soc Nephrol,2000, 11(4):717-728.
[73]Pecoits-Filho R, Araujo MR, Lindholm B, et al. Plasma and dialysate IL-6 and VEGF concentrations are associated with high peritoneal solute transport rate [J]. Nephrol Dial Transplant,2002,17(8):1480-1486.
[74]Stompor T, Zdzienicka A, Motyka M, et al. Selected growth factors in peritoneal dialysis: Their relationship to markers of inflammation, dialysis adequacy, residual renal function, and peritoneal membrane transport [J]. Perit Dial Int,2002,22(6):670-676.
[75]van Esch S, Zweers MM, Jansen MA, et al. Determinants of peritoneal solute transport rates in newly started nondiabetic peritoneal dialysis patients [J].Perit Dial Int,2004, 24(6):554-561.
[76]Szeto CC, Wong TY, Chow KM, et al. Dialysis adequacy and transport test for characterization of peritoneal transport type in Chinese peritoneal dialysis patients receiving three daily exchanges [J]. Am J Kidney Dis,2002,39(6):1287-1299.
[77]Zweers MM,Struijk DQSmit W,et al.Vascular endothelial growth factor in peritoneal dialysis:a longitudinal follow-up [J]. J Lab Clin Med,2001,137(2):125-132.
[78]张苗,蒋春明,孙净.黄芪对腹膜透析相关腹膜间皮细胞VEGF分泌和表达的影响[J].医 学临床研究,2005,22,(12)：1647-1650.
[79]Rodrigues A, Martins M, Santos MJ, et al.Evaluation of effluent markers cancer antigen 125, vascular endothelial growth factor, and interleukin-6:Relationship with peritoneal transport [J]. Adv Perit Dial,2004,20:8-12.
[80]Mandl-Weber S, Cohen CD, Haslinger B, et al. Vascular endothelial growth factor production and regulation in human peritoneal mesothelial cells [J]. Kidney Int,2002, 61(2):570-578.
[81]Szeto CC, Chow KM, Wong TY, et al.Feasibility of resuming peritoneal dialysis after severe peritonitis and Tenckhoff catheter removal [J]. J Am Soc Nephrol,2002,13(4): 1040-1045.
[82]De Vriese AS, Mortier S, Lameire NH. What happens to the peritoneal membrane in long-term peritoneal dialysis [J]. Perit Dial Int,2001,21 [Suppl 3]:S9-S18.
[83]Seo MJ, Oh SJ, Kim SI, et al. High glucose dialysis solutions increase synthesis of vascular endothelial growth factors by peritoneal vascular endothelial cells [J]. Perit Dial Int, 2001,21 Suppl 3:S35-40.
[84]Park SH, Lee EG, Kim IS, et al. Effect of glucose degradation products on the peritoneal membrane in a chronic inflammatory infusion model of peritoneal dialysis in the rat [J]. Perit Dial Int,2004,24(2):115-122.
[85]Eyries M, Collins T, Khachigian LM, et al. Modulation of growth factor gene expression in vascular cells by oxidative stress [J]. Endothelium,2004,11(2):133-139.
[86]Nilsson-ThorelⅠ CB, Muscalu N, Andren AH, et al.Heat sterilization of fluids for peritoneal dialysis gives rise to aldehydes [J]. Petit Dial Int,1993,13(3):208-213.
[87]Godbout JP, Pesavento J, Hartman ME, et al. Methylglyoxal enhances Cisplatin-indueed eytotoxicity by activating protein kinase Cdelta [J]. J Biol Chem,2002,277(4):2554-2561.
[88]Fan X, Subramaniam R, Weiss MF, et al. Methylglyoxal-bovine serum albumin stimulates tumor necrosis factor alpha secretion in RAW 264.7 cells through activation of mitogen-activating protein kinase, nuclear factor kappaB and intracell-ular reactive oxygen species formation [J]. Arch Biochem Biophys,2003,409(2):274-286.
[89]Ward RA, McLeish KR. Methylglyoxal:a stimulus to neutrophil oxygen radical production in chronic renal failure [J]. Nephrol Dial Transplant,2004,19(7):1702-1707.
[90]Aroeira LS, Aguilera A, Selgas R, et al. Mesenchymal conversion of mesothelial cells as a mechanism responsible for high solute transport rate in peritoneal dialysis:role of vascular endothelial growth factor [J]. Am J Kidney Dis,2005,46(5):938-948.
[91]Aquilera A, Aroeira LS, Ramirez-Huesca M, et al. Effects of rapamycin on the epithelial-to-mesenchymal transition of human peritoneal mesothelial cells [J]. Int J Artif Organs,2005,28(2):164-9.
[92]Mamputu JC, Renier G. Advanced glycation end products increase,through a protein kinase C dependent pathway,vascular endothelial growth factor expression in retinal endothelial cells.Inhibitory effect of gliclazide [J]. J Diabetes Complications,2002,16(4):284-293.
[93]Gunal AI, Celiker H, Akpolat N, et al.By reducing production of vascular endothelial growth factor octreotide improves the peritoneal vascular alterations induced by hypertonic peritoneal dialysis solution [J]. Petit Dial Int,2002,22(3):301-306.
[94]Zweers MM, de Waart DR, Smit W, et al. Growth factors VEGF and TGF-beta1 in peritoneal dialysis [J]. J Lab Clin Med,1999,134(2):124-132.
[95]Pawlaczyk K, Polubinska A, Numata N, et al. Vascular endothelial growth factor in dialysate in relation to intensity of peritoneal inflammation [J]. Int J Artif Organs,2008, 31(6):535-544.
[96]Leung JC, Chan LY, Tam KY, et al. Regulation of CCN2/CTGF and related cytokines in cultured peritoneal cells under conditions simulating peritoneal dialysis [J]. Nephrol Dial Transplant,2009,24(2):458-469.
[97]Pecoits-Filho R, Araujo MR, Lindholm B, et al. Plasma and dialysate IL-6 and VEGF concentrations are associated with high peritoneal solute transport rate [J]. Nephrol Dial Transplant,2002,17(8):1480-1486.
[98]Eckenstein FP. Fibroblast growth factors in the nervous system [J]. J Neurobiol,1994,25 (11):467-480.
[99]Muthukrishnan L,Warder E,Mcneil PL. Basic fibroblast growth factor is efficiently released from a cytolsolic storage site through plasma membrane disruption of endothelial cells [J]. J Cell Physiol,1991,148:1.
[100]Patsone G, Pasquale EB,Maher PA. Different mambrane of the fibroblast growth factor receptor family are specific to distinct cell types in the developing chicken embryo [J]. Dev Biol,1993,155:107.
[101]Philips GD, Schilb LA, Fiegel VD, et al. Angiogenic extract from skeletal muscle stimulates monocyte and endothelial cell chemotaxis in vitro [J]. Proc Soc Exp Biol Med, 1991,197:458.
[102]Marcus VC, Sylvis S, Helmut K, et al. Basic fibroblast growth factor synthesis by human peritoneal mesothelial cells induction by interleukin-1[J]. Am J Path,1999,155(6):1977-1984.
[103]刘映红,袁芳,肖平,等TGF-p1对人腹膜间皮细胞分泌细胞外基质和bFGF的影响[J].中国现代医学杂志,2002,12(14)：10-13.
[104]Chavakis T, Bierhaus A, Nawroth PP, et al. RAGE(receptor for advanced glycation end products):a central player in the inflammatory response [J]. Microbes Infect, 2004,6:1219-1225.
[105]陆福明,顾亢霞,郭晓敏等.终末期糖基化产物在尿毒症患者血清中的水平及血管壁和腹膜上的表达[J].中华肾脏病杂志,2000,16：147-151.
[106]Thornalley PJ. Advanced glycation end products in renal failure [J]. J Ren Nutr,2006,16: 178-184.
[107]Honda K, Nitta K, Horita S, et al. Accumulation of advanced glycation end products in the peritoneal vasculature of continuous ambulatory peritoneal dialysis patients with low ultrafiltration [J].Nephrol Dial Transplant,1999,14:1541-1549.
[108]Nakarnura S, Niwa T. Advaneed glycation end-products and peritoneal sclero-sis [J]. Semin Nephrol,2004,24(5):502-505.
[109]Nakayama M, Yoshimura K, Maruyama Y, et al. Possible involvement of cross-linking advanced glycation end products in long-term CAPD peritoneal degeneration [J]. Nephrol Dial Transplant,2004,19(6):1664-1665.
[110]De Vriese AS, Tilton RQ Mortier S, et al. Myofibroblast transdifferentiation of mesothelial cells is mediated by RAGE and contributes to peritoneal fibrosis in uraemia [J]. Nephrol Dial Trans Plant,2006,21(9):2549-2555.
[111]Boulanger E, Wautier MP, Gane P, et al.The triggering of human peritoneal mesothelial cell apoptosis and oncosis by glucose and glycoxydation products [J]. Nephrol Dial Transplant, 2004,19(9):2208-2216.
[112]Higuchi C, Nishimura H, Sanaka T. Biocompatibility of peritoneal dialysis fluid and influence of compositions on peritoneal fibrosis [J]. Ther Apher Dial,2006,10(4):372-379.
[113]DeYriese AS, Flyvbjerg A, Mortier S, et al. Inhibition of the interaction of AGE-RAGE prevents hyperglycemia-induced fibrosis of the peritoneal membrane [J]. J Am Soc Nephrol,2003,14(8):2109-2118.
[114]Schwenger V, Morath C,Salava A,et al. Damage to the peritoneal membrane by Glucose degradation produets is mediated by the receptor for advanced glycation end produets [J]. J Am Soc NePhrol,2006,17(1):199-207.
[115]Demir AY, Groothuis PG, Nap AW, et al. Menstrual effluent induces epithelial-mesenchymal transitions in mesothelial cells [J]. Hum Reprod,2004,19(1):21-29
[116]Ogata S, Yorioka N, Kohno N. Glucose and prednisolone alter basic fibroblast growth factor expression in peritoneal mesothelial cells and fibroblasts [J]. J Am Soc Nephrol, 2001,12(12):2787-2796.
[117]Ogata S, Naito T, Yorioka N, et al. Effect of lactate and bicarbonate on human peritoneal mesothelial cells, fibroblasts and vascular endothelial cells, and the role of basic fibroblast growth factor [J]. Nephrol Dial Transplant,2004,19(11):2831-2837.
[118]O'Reilly MS, Boehm T, Folkman J, et al. Endostatin:an endogenous inhibitor of angiogenesis and tumor growth [J]. Cell,1997,88(2):277-285.
[119]Hohenester E, Sasaki T, Olsen BR, et al.Crystal structure of the angiogenesis inhibitor endostatin at 1.5 A resolution [J]. EMBO J,1998;17(6):1656-1664.
[120]Standker L, Enger A, Schulz-Knappe P, et al.Structural and functional charac-terization of vitronectin-derived RGD-containing peptides from human hemofiltrate [J]. Eur Biochem, 1996,241:557-563.
[121]Dhanabal M, Ramchandran R, Volk R, et al.Endostatin:yeast production, mutants, and antitumor effect in renal cell carcinoma [J]. Cancer Res,1999,59(1):189-197.
[122]Ergun S, Kilic N, Wurmbach JH, et al.Endostatin inhibits angiogenesis by stabilization of newly formed endothelial tubes [J]. Angiogenesis,2001,4:193-206.
[123]Shichiri M, Hirata Y. Antiangiogenesis signals by endostatin [J]. FASEB J,2001,15: 1044-1053
[124]Yin G, Liu W, An P, et al. Endostatin gene transfer inhibits joint angiogenesis and pannus formation in inflammatory arthritis [J]. Mol Ther,2002,5(5 Pt 1):547-554.
[125]Berger AC, Feldman AL, Gnant MF, et al.The angiogenesis inhibitor, endostatin, does not affect murine cutaneous wound healing [J].J Surg Res,2000,91(1):26-31.
[126]Hanai J, Dhanabal M, Karumanchi SA, et al. Endostatin causes G1 arrest of endothelial cells through inhibition of cyclin D1 [J]. J Biol Chem,2002,277(19):16464-16469.
[127]Dhanabal M,Ramchandran R,Waterman MJ, et al. Endostatin induces endothelial cell apoptosis [J]. J Biol Chem,1999,274(17):11721-11726.
[128]Kim YM, Jang JW, Lee OH, et al. Endostatin inhibits endothelial and tumor cellular invasion by blocking the activation and catalytic activity of matrix metalloproteinase [J]. Cancer Res,2000,60(19):5410-5413.
[129]Macdonald N J, Shivers WY, Narum DL, et al. Endostatin binds tropomyosin. A potential modulator of the antitumor activity of endostatin [J]. J Biol Chem,2001,276(27): 25190-25196.
[130]Rehn M, Veikkola T, Kukk-Valdre E, et al. Interaction of endostatin with integrins implicated in angiogenesis [J]. Proc Natl Acad Sci USA,2001,98(3):1024-1029.
[131]Kim YM, Hwang S, Kim YM, et al. Endostatin blocks vascular endothelial growth factor-mediated signaling via direct interaction with KDR/Flk-1[J]. J Biol Chem,2002, 277(31):27872-27879.
[132]Walgenbach KJ, Gorospe JR, Gratas CA. Potential role for mast cells in the release of bFGF from normal myocytes during angiogenesis in vivo [J]. J Invest Surg 2002, 15(3):153.
[133]Nissen NN, Polverini PJ, Koch AE, et al. Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing [J]. Am J Pathol,1998, 152(6):1445-1452.
[134]Ryuto M, Ono M, Izumi H. Induction of vascular endothelial growth factor by tumor necrosis factor alpha in human glioma cells.possible roles of SP-1 [J]. J Bio Chem,1996, 271(45):28220.
[135]Pepper MS, Mandriota SJ, Vassalli JD, et al. Angiogenesis regulating cytokines:actions and interactions [J]. Curr Top Microbiol Immunol,1996,213:31.
[136]Funatsu H, Yamashita H, Noma H, et al. Stimulation and inhibition of angiogenesis in diabetic retinopathy [J]. Jpn J Ophthalmol,2001,45:577-584.
[137]Sasaki T, Larsson H, Kreuger J, et al. Structure basis and potential of heparin/hepatan sulfate binding to the angiogenesie inhibitor endostatin [J].Embo J,1999,18(22):6240-6248
[138]Ribatti D. The seminal work of Werner Risau in the study of the development of the vascular system [J]. Int J Dev Biol,2010,54(4):567-572.
[139]Przybylski M. A review of the current research on the role of bFGF and VEGF in angiogenesis [J]. J Wound Care,2009,18(12):516-519.
[140]Dai H, Zhao S, Xu L, et al. Expression of Efp, VEGF and bFGF in normal, hyperplastic and malignant endometrial tissue [J]. Oncol Rep,2010,23(3):795-799.