摘要
目的
本课题以中医“痰瘀互结”是腹膜纤维化发生的病机关键为理论依据,采用临床与动物实验相结合的方法,观察并探讨化痰祛瘀法防治腹膜透析患者腹膜纤维化的临床效果。并重点从TGF-β/Smads信号通路,进一步探讨化痰祛瘀法防治腹膜纤维化大鼠模型的作用和机制。综合评价化痰祛瘀法防治腹膜纤维化的临床疗效,为防治腹膜透析患者腹膜纤维化提供新的中医药理论依据与方法。
方法
通过收集我院2010年1月至2011年1月符合纳入标准的腹膜透析患者,观察化痰祛瘀中药对腹膜透析患者的临床症状及实验室指标如血肌酐、尿素氮、白蛋白、血脂、血分析、肝纤四项及腹透液中TGF-β1、VEGF因子表达等的影响,客观评价化痰祛瘀中药防治腹膜纤维化的临床疗效。
通过建立大鼠腹膜纤维化模型,观察经用化痰祛瘀中药干预后,腹膜纤维化大鼠模型腹膜结构的组织学变化,阐明化痰祛瘀中药拮抗腹膜纤维化大鼠模型的有效性。并应用间接免疫荧光法测定各组大鼠壁层腹膜TGF-β1、p-Smad2/3和α-SMA、E-cadherin及p-Smad7蛋白的表达,探讨化痰祛瘀中药拮抗腹膜纤维化与调控TGF-β/Smads信号通路的关系,初步揭示化痰祛瘀法防治腹膜纤维化的作用机制。
结果
(一)化痰祛瘀法防治腹膜纤维化的临床研究
1、化痰祛瘀中药对中医症候积分的影响
治疗组经用化痰祛瘀中药治疗后,面色晦暗,肌肤甲错,肢体麻木或刺痛,身重困倦,脘腹胀满,口中粘腻,口干不欲饮,食少纳呆,大便粘滞不爽的改善作用明显优于对照组(P<0.05),表明化痰祛瘀中药在改善中医痰瘀互阻症候方面,治疗组优于对照组。
2、化痰祛瘀中药对腹膜纤维化相关指标的影响
治疗组疗后腹透液中TGF-β1因子水平显著下降(130.56±14.54 pg/ml),与治疗前相比(164.84±32.38 pg/ml),有显著性差异(P<0.05);对照组治疗前好比较无显著性差异(P>0.05),治疗后,两组组间比较,治疗组腹透液中TGF-β1因子下降水平明显高于对照组(P<0.01)。
治疗组疗后腹透液中VEGF因子水平显著下降(63.62±12.95pg/ml),与治疗前相比(95.87±18.59pg/ml),有显著性差异(P<0.05);对照组治疗前好比较无显著性差异(P>0.05),治疗后,两组组间比较,治疗组腹透液中VEGF因子下降水平明显高于对照组(P<0.01)。
反映纤维化程度的指标:肝纤四项,治疗组与对照组疗后与疗前比较,均有所降低,但仅治疗组差异有统计学意义(P<0.05),对照组差异无统计学意义(P>0.05);治疗后,两组组间比较,统计学有显著性差异(P<0.01);表明腹膜透析患者服用化痰祛瘀中药对肝纤四项指标有一定的改善作用。
3、化痰祛瘀中药对实验室指标的影响
治疗组经用化痰祛瘀中药治疗后,治疗组的肌酐、尿素氮、总胆固醇、甘油三酯、低密度脂蛋白、纤维蛋白原等指标的改善作用优于对照组(P<0.05),表明化痰祛瘀中药在改善患者肾功能、血脂、凝血功能方面,有良好疗效。
4、化痰祛瘀中药药物安全性指标的观察
治疗组患者服用化痰祛瘀中药期间,未出现各种不良反应症状,反映心脏功能、肝功能的指标肌酸激酶-MB同工酶(CK-MB).谷草转氨酶(AST)、谷丙转氨酶(ALT)、谷氨酰转移酶(GGT),治疗前后,差异无统计学意义(P>0.05),表明腹膜透析患者服用化痰祛瘀中药,对心脏及肝功能无不良影响,服用安全。
(二)化痰祛瘀法防治腹膜纤维化的实验研究
1、腹膜间皮细胞内存在TGF-β1、Smad2/3、Smad7、SMA和E-cadherin蛋白的表达,并证实高浓度葡萄糖透析液和LPS有协同作用,能促进大鼠腹膜组织TGF-G1/Smads信号通路的活化,产生更加明显的腹膜纤维化。
2.TGF-β1/Smads信号通路是腹膜纤维化的共同作用途径,化痰祛瘀中药是通过对TGF-β/Smads信号通路的影响来拮抗腹膜纤维化的,中药高剂量组有更好的防治腹膜纤维化的作用。
3、化痰祛瘀中药能上调TGF-β抑制性信号蛋白Smad7的表达,这可能是通过抑制TGF-β受体调控信号蛋白(Smad2/3)的活化,还显示化痰祛瘀中药能减轻E—cadhefin蛋白水平下调,及α-SMA蛋白水平上调的程度,进而说明化痰祛瘀中药可以减轻腹膜间皮细胞转分化的程度,防止腹膜纤维化的发展,保护腹膜功能。
结论
1、通过对2010年1月至2011年1月符合纳入标准的30例行标准连续性非卧床腹膜透析(CAPD)治疗者临床研究提示:化痰祛瘀中药可以改善腹膜透析患者临床症状,提高腹膜透析治疗效果。
2、化痰祛瘀中药复方能明显降低反映腹膜纤维化的相关指标(肝纤四项、腹透液中TGF-β1、VEGF因子),可以明显减轻腹膜纤维化大鼠模型腹膜组织的炎症反应病理改变程度,保护腹膜组织形态结构的完整,减少腹膜纤维化大鼠模型腹膜的致密层厚度,从而起到拮抗腹膜纤维化的作用,这一作用呈量效关系,以中药高剂量组效果最佳。初步显示化痰祛瘀中药有较好的防治腹膜纤维化作用。
3、通过对5/6肾切除的大鼠应用4.25%的高糖腹膜透析液和脂多糖(LPS)造成腹膜纤维化模型的研究发现:化痰祛瘀中药拮抗腹膜纤维化的作用机制可能是通过上调TGF-β抑制性信号蛋白Smad7的表达,进而抑制TGF-β受体调控信号蛋白(Smad2/3)的活化,阻止腹膜纤维化动物模型腹膜间皮细胞转分化的发生,从而阻止或减轻腹膜纤维化的发生和进展,保护腹膜功能。
Objective
The topics to Chinese medicine, "the phlegm stasis ties mutually" is the pathogenesis key which the peritoneum fibrosis occurs as the theoretical basis, Uses the clinical method which unifies with the animal experimentation, observes and discusses the phlegm reduction to remove extravasted blood the law prevention in peritoneal dialysis patients the clinical effect. And key from TGF-β/Smads signal passage, further discusses the phlegm reduction to remove extravasted blood the law prevention peritoneum fibrosis big mouse model the function and the mechanism. Comprehensive evaluation of the use of phlegm and blood stasis and the prevention and treatment of peritoneal fibrosis in clinical efficacy for the prevention of peritoneal fibrosis in peritoneal dialysis patients to provide a new theoretical basis and methods of Chinese medicine.
Methods
Through the collection of our hospital from January 2010 to January 2011 met the inclusion criteria of the peritoneal dialysis patients Phlegm and blood stasis observed in patients on peritoneal dialysis clinical symptoms and laboratory parameters such as serum creatinine, urea nitrogen, albumin, blood lipids, blood analysis, liver filament four item and peritoneal fluid TGF-β1, VEGF expression factor such as the impact of phlegm and blood stasis objective evaluation of the clinical efficacy of prevention and treatment of peritoneal fibrosis. Through the establishment of big mouse peritoneum fibrosis model, after the observation durable phlegm reduction removes extravasted blood the traditional Chinese medicine intervention, the peritoneum fibrosis big mouse model peritoneum structure's histology change, expounded that the phlegm reduction removes extravasted blood the traditional Chinese medicine to oppress the anti-big mouse model peritoneum fibrosis the validity
And applies the indirect immunity fluorescence method to determine each group of big mouse somatopleura peritoneum TGF-β1, p-Smad2/3 andα-SMA, E-cadherin and the p-Smad7 protein expression, the discussion phlegm reduction removes extravasted blood the traditional Chinese medicine to oppress the anti-peritoneum fibrosis and the regulative TGF-β/Smad signal passage's relations, promulgates the phlegm reduction to remove extravasted blood the law prevention peritoneum fibrosis initially the function mechanism.
Result
(一) The phlegm reduction removes extravasted blood the law prevention peritoneum fibrosis the clinical research
1、Phlegm and blood stasis syndrome influnce score of Chinese medicine After the treatment group durable phlegm reduction removes extravasted blood the traditional Chinese medicine treatment, the facial color is gloomy, the flesh armor is wrong, the body numb or the stabbing pain, the feeling of heaviness in the limbs is sleepy, wan abdomen puffiness, in the mouth sticks greasily, dry mouth do not want to drink, the food few losses of appetite, stool viscosity the improvement function surpasses the control group obviously (P<0.05), whichshow phlegm reduction removes extravasted blood the traditional Chinese medicine to improve the symptoms, the treatment group better than the control group.
2、Phlegm and blood stasis related indicators of the impact of peritoneal fibrosis
Effluent treatment group after treatment factors in the TGF-β1 levels decreased significantly (130.56±14.54 pg/ml), compared with before treatment (164.84±32.38 pg/ml), there was significant difference (P<0.05); the control group Good pre-treatment showed no significant difference (P> 0.05), after treatment, comparison between the two groups, treatment group, dialysate factor in the decreased levels of TGF-β1 was significantly higher (P<0.01).
Effluent treatment group after treatment factors in the VEGF levels were significantly decreased (63.62±12.95pg/ml), compared with before treatment (95.87±18.59pg/ml), there was significant difference (P<0.05); the control group before treatment well there was no significant difference (P>0.05), after treatment, comparison between the two groups, the treatment group factor of decline in peritoneal dialysis fluid VEGF levels were significantly higher (P<0.01).
Indicators reflect the degree of fibrosis:hepatic-fibrosis four, treatment and control groups before treatment after treatment compared were decreased, but only statistically significant difference between the treatment group (P<0.05), no statistical difference between the control group significance (P>0.05); after treatment between the two groups was statistically significant difference (P<0.01); showed that patients treated with peritoneal dialysis on liver blood stasis Phlegm fiber four indicators have some improvement.
3、Phlegm and blood stasis effect on laboratory parameters
Treatment group after treatment with phlegm and blood stasis, the i mprovement of creatinine, urea nitrogen, total cholesterol, triglycerides, low density lipoprotein, fibrinogen better than the control group (P<0. 05), indicating that the phlegm and blood stasis in improving renal funct ion, blood lipid, have a good effect.
4、Phlegm and blood stasis observed indicators of drug safety
Treatment group, reflecting the heart and liver function indicators of CK-MB, AST, ALT, GGT, before and after treatment, the difference was not statistically significant (P>0.05), showed that patients treated with peritoneal dialysis phlegm and blood stasis, on cardiac function and liver no functional effect, taking safety.
(二) Experimental study of phlegm and blood stasis to Prevent and Treat the peritoneal fibrosis
1、Peritoneal mesothelial cells exist in TGF-β1, Smad2/3, Smad7, SMA, and E-cadherin protein expression, and confirmed that high glucose dialysate and LPS have synergistic effects, can signal in rat peritoneal tissue TGF-β1/Smads pathway activation, resulting in more significant peritoneal fibrosis.
2、TGF-β1/Smads signaling pathway is a common pathway of peritoneal fibrosis, phlegm and blood stasis TGF-β/Smad signaling pathway through the influence of antagonistic to peritoneal fibrosis, the Chinese high-dose group had a better prevention and treatment of peritoneal fibrosis.
3、phlegm and blood stasis can increase TGF-βinhibitory Smad7 expression of signaling proteins, which may inhibit the regulation of TGF-βreceptor signaling protein (Smad2/3) activation, also showed that blood stasis can reduce phlegm E-cadhefin lower protein levels, and increased levels ofα-SMA protein level, then explain the phlegm and blood stasis can reduce the transdifferentiation of peritoneal mesothelial cells in the extent and prevent the development of peritoneal fibrosis, peritoneal membrane function protection
Conclusion
1、Through January 2010 to January 2011 30 patients met the inclusion criteria of the standard continuous ambulatory peritoneal dialysis (CAPD) treatment of clinical studies suggest that:phlegm and blood stasis can improve clinical symptoms of peritoneal dialysis patients, increased peritoneal dialysis treatment
2、Blood stasis and phlegm reflect the:compound can significantly reduce the relevant indicator of peritoneal fibrosis (liver fiber four, peritoneal fluid TGF-β1, VEGF factor), can protect the structural integrity of peritoneal morphology and reduce the rat model of peritoneal fibrosis, peritoneal thickness of the dense layer, play the role of peritoneal fibrosis antagonist. Phlegm and blood stasis initially showed better prevention and treatment of peritoneal fibrosis.
3, Through 5/6 nephrectomy rats application of 4.25% of the high-glucose peritoneal dialysis fluid and lipopolysaccharide (LPS) caused by retroperitoneal fibrosis were found:phlegm and blood stasis on the impact of TGF-β/Smad signaling pathway possibly by increased TGF-βsignaling inhibition protein expression of Smad7 and inhibit TGF-βreceptor signaling protein regulated (Smad2/3) activation, prevents peritoneal fibrosis in animal models of peritoneal mesothelial cell transdifferentiation occurs, thereby preventing or reducing the incidence and progression of peritoneal fibrosis, Protection of peritoneal function.
引文
[1]汪涛,王英.腹膜透析的现状,2002,25(2):13-15
[2]余学清.中国腹膜透析现状及思考.中国中西医结合肾病杂志,2005,6(1):1-2
[3]Shimaoka T, Hamada C, Kaneko K, etal. Quantitative evaluation and assessment of peritoneal morphologic changes in peritoneal dialysis patients[J]. Nephrol Dial Transplant,2010 Apr 22.
[4]Nessim SJ, Perl J, Bargman JM.The renin-angiotensin-aldosterone system in peritoneal dialysis:is what is good for the kidney also good for the peritoneum?[J]. Kidney Int,2010,78:23-28.
[5]Breborowicz A, RodelaH, Oreopeulos DG. Toxicity of osmotic solutes on human mesothelial ceLls in vitro. Kidney International,1992。41(5):1280.
[6]Catwzzi s, Nasini MG, Schelotto C etal. A biocomp afibflity studyon peritoneal dialysis solution hays for CAPD. Advperit Dial.1993。 9:138.
[7]Topley N, Williams JD. Efectof peritonealdialysison cytokineproduction by peritoneal cells. Blood Purif,1996,14:188-197.
[8]ShostakA, Pivnik K, Gotloib L. Daly short exposure of cutured mesothelial cells to lactated, high glucose, low pH peritoneal dialysis fluid induces a low—profile regenerative steady state. Nehrol Dial Transplant,1996,11: 608-613.
[9]Stojimirovi B, Trpinac D, Obradovi M, etal. Changes in peritoneal mesothelial cells in patients on peritoneal dialysis. Med Pregl,2001,54(5-6):219-230.
[10]Krediet RT. The peritoneal membrance in chronic peritoneal dialysis patients. Kidney Int,1999,55:341-356.
[11]唐知还,腹膜透析液对于腹膜间皮细胞的影响.中国血液净化,2003,2(3):151—154.
[12]Gokal R. New strategies for peritoneal dialysis fluids. Nephrol Dial Transplant,1997,12(Suppl 1):74-77.
[13]侯凡凡.臧燕.张训.等.高浓度葡萄糖对人腹膜问皮细胞生长和基质合成的影响.中华内科杂志,1995,34(5):326-329
[14]董柯.陈香美.傅博.等.高渗葡萄糖对腹膜透析感染影响的机理研究.中华医院感染学杂志,1996,6(4):209-211
[15]Harvey W, Amlot PL. Collagen production by human mesothelial cells in vitro. J Pathol,1983,139(3):337-347
[16]杨泽然.李继承.张凯.等.腹膜透析液对腹腔巨噬细胞产生一氧化氮和细胞活力的影响.浙江大学学报(医学版),2002,31(1):23-25
[17]Takafumil. Nodaki Y, MasaoY, et al. Effect of Glucose on Intercelular Junctions of Cultured Human Peritoneal Mesothelial Cells. J Am Soc Nephrol, 2000,11:1969-1979.
[18]Marcus Victor Cronauer, Sylvia Stadlmann, Helmut Klocker, et al. Basic Fibroblast Growth Factor Synthesis by Human Peritoneal Mesothelial Cells. American Joumal of Pathology,1999,155:1977-1984.
[19]Jones A, BenderTO, Firm A, et al. Biocompatibility and bufers:effect of bicar-bonate-buffered peritoneal dialysis fluidson peritoneal cell function. Kidney lnt,1998,54:2184-2193.
[20]Breborowicz A,et al.Perit Dial Int,1995;15(suppl 1):68
[21]LaiKN, Leung JC, Chan LY, et a.1 Differential expression of recptors for advanced glycation end-products in peritoneal mesothelial cells exposed to glucose degradation products[J].Clin Exp Immunol,2004,138(3):466-475.
[22]HondaK, NittaK, Horita S, eta.1 Accumulation ofadvanced glycation end products in the peritoneal vasculature of continuous ambulatory peritoneal dialysis patientswith low ul tra-filtrat ion [J]. Nephrol Dial Transplant,1999, 14(6):1541-1549.
[23]Lamb EJ, Cattell WR, Dawnay AB. In vitro formation of advanced glycation end products in peritoneal dialysis fluid. Kidney Int,1995,47(6):1768-1774.
[24]SchwengerV, Morath C, Salava A, et al. Damage to the peritoneal membrane by glucose degradation products ismediated by the receptor for advanced glycation end-products[J]. J Am Soc Nephrol,2006,17(1):199-207.
[25]Breborowicz A, Oreopoulos D G. Evidence for the Presence of Chronic Inflammation During Peritoneal Dialysis:Therapeutic Implications [J]. Perit Dial Int,1997,17:$37-$41.
[26]Peeoits-Filhob R,Stenvinkel P. Chronic Inflammation in Peritoneal Dialysis:the Search for the holy grail?[J]. Perit Dial Int,2004,24:327- 339.
[27]Betjes MGH, etal.KidneyInt,1993.43:641-648
[28]Betjes MG, et al. Perit Dial Int.1991,11(1):22-26
[29]文琼,余学清,黄昭,等.转化生长因子β 1诱导肾小管上皮细胞转分化的蛋白质组学研究[J].中华肾脏病杂志,2008,24(1):18-23.
[30]Sakamoto N, Sugimura K, Kawashima H, etal. Influence of glucose and inflammatory cytokines on TGF-lbeta and CTGF mRNA expressions in human peritonealmesothelial cells[J]. IntJ MolMed,2005,15(6):907-911.
[31]李建飞,刘伏友,彭佑铭等.短发夹结构RNA对人腹膜间皮细胞转化生长因子β1表达和超微结构的影响[J].中国血液净化,2007,6(9):490-495.
[32]BraunnerA.etal.Am J Kindney Dis,1996,27(3):402-428
[33]刘宏发.CAPDI时腹膜状态标志物[J].医学综述,1999,5(6):274
[34]Brauner A, etal. Am J Kindney Dis,1993,22(3):430-435
[35]Braunner A. etal. Am J Kindney Dis,1996,27(3):402-428
[36]Zemel D. etal. Perit Dial lnt,1995.15:134-141
[37]Yanez-Mo M, Lara-Pezzi E.Selgas R, et al. Peritoneal dialysis an d epithelial-to-mesenchymal transition of mesothelial cell [J]. N Engl J Med,2003,348 (5):403-413
[38]Aroeira L S,Aguilera A.Sanchez-Tomero J A, et al. Epithelial to m esenchymal transition and peritoneal membrane failure in peritoneal dialy sis patients:pathologic significance and potential therapeutic interven tions[J]. J Am Soc Nephrol,2007,18(7):2004-2013.
[39]Jimenez-HeffernanJA, AguileraA, Aroeira LS, etal. Immunohistochemical cha racterization of fibroblast subpopulations in normal peritoneal tissueand in peritoneal dialysisinduced fibrosis. Virchows Arch,2004,444(3):247-256.
[40]DelPesoG, Jimenez-HeffernanJA, BajoMA, etal. Epithelial-to-mesenchymal tr ansition of mesothelial cells is an early event during peritoneal dialysi s and is associated with high peritoneal transport. Kidney Int Suppl,2008, 108:26-33.
[41]Ikenouchi J, Matsuda M, Furuse M, etal. Regulation of tight junctions dur ing the epithelium-mesenchyme transition:direct repression of the gene ex pression of claudins/occludin by Snail. J Cell Sci,2003,116(10):1959-1967.
[42]Utepbergenov DI, Fanning AS, Anderson JM. Dimerization of the scaffoldi ng protein ZO-1 through the second PDZ domain. J Biol Chem,2006,281(34):24 671-24677.
[43]李荟.肾小管上皮细胞-间充质细胞转分化在肾间质纤维化中的作用.国外医学·泌尿系统分册,2005,25(3):426-429.
[44]Jimenez—Hefeman JA, Aguilera A, Aroeim LS, et al. Immunohistochemical characterization of fibroblast subpopulations in normal peritoneal tissue and in peritoneal dialysis—induced fibrosis. Virchows Arch,2004,444:247-256.
[45]姚俊霞,吴人亮.肾小管上皮细胞转分化与肾小管间质纤维化.中国现代医学杂志,2008,18(11):1561-1564.
[46]Liu Y. Epithelial to mesenchymal transition in renal fibrogenesis:Path ologic significance, molecular mechanism, and therapeutic intervention. JAm Soc Nephrol,2004,15(1):1-12.
[47]Fujigaki Y, Sun DF, Fujimoto T, et al. Mechanisms and kinetics of Bowman' s epithelial-myofi broblast transdifferentiation in the formation of glom erularcrescents. Nephron,2002,92 (1):203-212.
[48]Yanez·Mo M, Lara · Pezzi E, Selgas R, et al. Petitoneal dialysis and Epithelial-to-mosenchymal transition of mesothelial ceHs. N Engl JMed,2 003 。 348:403-413.
[49]Jimenez—Hefeman JA, Aguilera A, hxoeim Ls, el a. Immunohistochemical characterization of fibroblast subpopulations in norm al petitoneal tissu e and in petitoneal dialysis-induced fibrosis. Vivchows Arch,2004,444:2 47-256.
[50]Liu Y. Epithelial to mesenchymal transition in renal fibrogenesis:P athologic significance, molecular mechanism, and therapeutic intervention [J]. J Am Soc Nephrol,2004,15(1):1-12
[51]Martin J, Yung S, Robson RL, et al. Production and regulation Of matr ix metalloproteinases and their inhibitors by human peritoneal mesothelia 1 cells. Perit Dial Int,2000, (5),524-533
[52]Nagy JA. Kidney Int,1996;50(Suppl 56):2-11
[53]刘映红,袁芳,肖平,等.TGF-β对人腹膜间皮细胞分泌细胞外基质和bFGF的影响.中国现代医学杂志,2002,12(14):10-13.
[54]Shi Y, Massague J. Mechanisms of TGF-beta signaling fram cell membrane to the necleus. Cell,2003,113(6),685-700
[55]Liu YH, liuFY, Zhang H. Efect of High Glucose on the Cell Proliferation, Damage and Cytokine in Human Peritoneal Mesothelial Cells [J]. Medical Journal Zhergnan Univercity,2006,31(4):575-579.
[56]LiuFY, Duan SB, LOllgZG. Culture and characterization of human peritoneal mesothelial cells. Hunan Yi Ke Da Xue Xue Bao,2001,26(4),321-324
[57]Medealf JF, Walls J, Pawluczyk, et al. Efects Of glucose dialysate on extracellular matrix production by human peritoneal mesothalial cells (HPMC): the role of TGF-beta. Nephrol Dial Transplant,2001,16(9),1885- 1892
[58]Wong TY, Phillips A0, Witowski J, et al. Glucose-mediated induction of TGF-betal andMCP-1 in mesothelial cells in vitrois osmolality and polyol pathway dependent. Ki Int,2003,63(4),1404-1416
[59]Naiki Y, Maeda Y, Matsuo K, et al. Involvement Of TGF-beta signal for peritoneal sclerosing in continuous ambulatory peritoneal dialysis. J Nephrol, 2003,16(1),95-102
[60]Al-Jayyonsi R, Medcalf JF, Harris KP. Role of transforming growth factor beta in peritoneal fibrosis. Nephrology,2002,7,216-219
[61]Zarrinkalam KH, Stanley JM, Gray J, et al. Connective tissue growth factor and its regulation in the peritoneal cavity of peritoneal dialysis patients [J]. Kidney Int,2003,64(1):331-338
[62]Liu Y:Epithelial to mesenchymal transition in renal fibrogenesis:P athologic significance, molecular mechanism and therapeutic intervention[J] JAm Soc Nephrol,2004,15(1):1-12.
[63]Qi w.Chen x, Polhill TS, etal. TGF-betal induces L-8 and MCP-1 through a connective tissue growth factor-independent pathway [J]. Am J Physiol Renal Physiol,2006,290(3):F703-F709.
[64]Leask A, Abraham DJ. The role of connective tissue growth factor, a multifunctional marticellular protein, in fibroblast biology [J]. Biochem Cell Biol,2003,81(6):355-363.
[65]Blom IE, van Dijk AJ, Wieten L, et al. In vitro evidence for diferenti al involvement of CTGF, TGFfl, and PDGF-BB in mesangial response to injury [J]. Nephrol Dial Transplant,2001,16:1139-1148.
[66]Fan WH, Pech M, Karnovsky MJ. Connective tissue growth factor (CTGF) stimulates vascular smooth muscle cell growth and migration in vitro [J]. Eur J Cell Biol,2000,79:915-923.
[67]Guha M, Xu ZG, Tung D, etal. Specific down—regulation of connective tissue growth fact attenuates progression of nephropathy in mouse models of type 1 and type 2 diabetes[J]. FASEB J,2007,21(12):3355-3368.
[68]Liu N, shimizu S, Ito-Ihara T, etal. AngiotensinⅡ receptor blockade ameliorates mesangioprolliferative glomerulonephritis in rats through suppression of CTGF and PAI-1, independendy of the coagulation system [J]. Nephron Exp Nephrol,2007,105(3):E65-E74.
[69]Ohshim Y, Ma Rc. Yasuda Y, etal. Reduction of diabetes—induced oxidative stress, fibrotic cytokine expression, and renal dysfunction in protein kinase C beta-null mice[J]. Diabets,2006,55(11):3112-3120.
[70]Suzuma K, Naruse K, Suzuma I, etal. Vascular endothelial growth factor induces expression of connective tissue growth factor via KDR, Fltl, and phosphatidylinositol 3-kinase-akt-dependent pathways in retinal vascular cells [J]. J BioJ chem,2000,275(52):4072-40731.
[71]MatsudaS, Gomi F, katayama T, etal. Induction of connective tissue growth factor in retinal pigment epithelium cells by oxidative stress [J]. Jpn J Ophthlalmol,2006,50(3):229-234.
[72]AlbrektssonL A, Bazargani F, Wieslanderl A, etal. Peritoneal Dialysis Fluid-Induced Angiogenesis in Rat Mesentery Is Increased by Lactate in the Presence or Absence of Glucose[J]. ASAIO J,2006,52(3):276-281.
[73]Williams JD,Craig K J, von RhulandC,et al.The Natural Course of Peritoneal Membrae Biology During Peritoneal Dialysis[J], Kidney Int,2003,64(88): S43-S44.
[74]Yoshio Y,Miyazaki M,Abe K,et al. Suppresses the Progression of Peritoneal Fibrosis in Mouse Experimental Model[J]. Kidney Int,2004,66:1677-1685.
[75]Motomura Y, Kanbayashi H, Khan W I, et al. The Gene transfer of soluble VEGF type I receptor (Fit-1) Attenuates Peritoneal Fibrosis Formation in Mice but Not Soluble TGF—beta type II Receptor Gene Transfer [J]. Am J Physiol Gas —trointest Liver Physiol,2005,288:G143—G150.
[76]Mateijsen MA, van der WalAC. Vascular and interstitial changes in the peritoneum of CAPD patients with peritoneal sclerosis [J]. PeritDial Int,1999, 19(6):517-525.
[77]Liu FY, Xiao L, PengYM, et al. Inhibition effect of small interferingRNA of connective tissue growth factor on the expression of vascular endothelialgrowth factor and connective tissue growth factor in cultured human peritonealmesothelial cells[J]. ChinMed J(Engl),2007,120(3):231-236
[78]SelgasR, BajoA, Ji e nez-Hefferman JA, etal. Epithelial-to-mesen-chymal transition of themesothelial cell—its role in the response of the peritoneum to dialysis[J]. NephrolDialTransplant,2006,21 (Supp12):112-117.
[79]DeVrieseAS, Mortier S, Lameire NH. Glucotoxicity of the peritoneal membrane:the case for VEGF[J]. Nephrol Dial Transplant 2001,16(12): 2299-2302.
[80]AroeimLs,AguileraA,Selgas R,el al.Mesenchymal conversion of mesothelial eels as a mechanism responsible for high solute transport rate in peritoneal dialysis:Role of vascular endothelial growth factor[J].Am J Ki dney Dis, 2005,46:938-948.
[81]Mandl—WeberS, CohenCD, HaslingerB, elal. Vascular endothelial growth factor production and regulation in human peritoneal mesothelial cels. KidIley Int,2002,61:570-578.
[82]Aguilera A, Yanez-MoM, Selgas R, et al. Epithelial tomesenchyrmal transition as a triggering factor of peritonealmembrane fibrosis and angiongenesis in peritonealdialysis patients[J]. CurrOpin InvestigDrugs,2005,6(3):262-268.
[83]Devuyst 0, Topley N, Williams JD. Morphological and functional changes in the dialysed peritoneal cavity:impact ofmore biocompatible solutions[J]. Nephrol Dial Transplant,2002,17 (Supp13):12-15.
[84]Abha S, Charles WF. Vascular endothelial growth factor binds to fibrinogen and fibrin and stimulates endothelial cell proliferation [J]. Blood,2000, 96(12):3772-3778.
[85]Brown KJ, MaynesSF, BezosA, etal. A novel in vitro assay for human angiogenesis[J].Lab Invest,1996,75(4):539-555.
[86]Nessim SJ, Perl J, Bargman JM. The renin-angiotensin-aldosterone system in peritoneal dialysis:is what is good for the kidney also good for the peritoneum?[J]. Kidney Int,2010,78:23-28.
[87]WolfC,Neilson EG. Angiotensin I1 as a renal growth factor. JAmSoc Nephrol, 1993,3(9):1531-1540.
[88]Deferrari G, Ravera M, Deferrari L, et al. Renal and cardiovascular protection in type 2 diabetes mellitus:angiotensin II receptor blockers. J Am Soc Nephrol,2002,13(Suppl 3):S224—S229.
[89]Delbaere A, BergmmmPJ, Gervy—DecosterC, etal. Petiovulatory elevation of angiotensin I1 in the peritoneal fluid during the human menstrual cycle. J Clin Endocrinol Metab,1996,81(8):2810-2815.
[90]Kiribayashi K, Masaki T, NaitoT, etal. Angiotensin 1I induces fibmnectin expression in human peritoneal mesothelial cells via ERK1/2 and p38 MAPK. Kidney Int,2005,67(3):1126-1135.
[91]Wu J, Yang X, Zhang YF, et al. Angiotensin II upregulates Toll-like receptor 4 and enhances lipopolysaccharide-induced CD40 expression in rat peritoneal mesothelial cells[J]. Inflamm Res,2009,58:473-482.
[92]Noh H, Ha H, YuMR, etal. Angiotensin I1 mediates high glucose—induced TGF — betal and fibronectin upregulation in HPMC through reactive oxygen species. Petit Dial Int,2005,25 (1):38-47
[93]Nakamoto H, Irrai H, Fukushima R, et al. Role of the renin-angiotensin system in the pathogenesis of peritoneal fibrosis [J].Perit Dial Int,2008,28 Suppl 3:S83-87.
[94]Fujiyama S, Matsubara H, Nozawa Y, etal. Angiotensin AT(1) and AT(2)r eceptors differentially regulate angiopoietin—2 and vascular endothelial growth factor expression and angenesis by modulating heparin binding-epi dermal growth factor (EGF) — mediated EGF receptor transactivation. Circ Re s,2001,88(1):22-29
[95]KyudenY, hoT, MasakiT. Tgf-betal Induced by High Glucose is Controlled by Angiotensin-converting Enzyme Inhibitor and Angiotensin II Receptor Blocker on Cultured Human Peritoneal Mesothelial Cells[J]. Perit Dial Int, 2005,25(5):
[96]Duman S, Gunal AI, Sen S, Does Enalapril Prevent Peritoneal Fibrosis Induced byHypertonic(3.86%)Peritoneal Dialysis Solution?[J]. Perit Dial Int,2001, 21(2):219-224
[97]DumanS, Wieczorowska—TobisK, Styszynski A. Intraperitoneal Enalapril Ameliorates Morphologic Changes Induced by Hypertonic Peritoneal Dialysis So lutions in Rat Peritoneum [J]. Adv Perit Dial,2004,20:31-36.
[98]Sauter M, Cohen CD, Worule M, el al. ACE inhibitor and AT1-receptor blocker attenuate the production of VEGF in mesothelial cells. Petit Dial Int.2007, 27:167-172
[99]Sauter M, Cohen CD, Wornle M, et al.ACE inhibitor and AT1-receptor blocker attenuate the production of VEGF in mesothelial cells[J]. Perit Dial Int,2007,27:167-172.
[100]刘伏友.腹膜透析腹膜纤维化的机制及防治.中国血液净化,2007,6(12):640-642.
[101]Adachi Y, Nakagawa Y, Nishio A. Icodextrin preserves residual renal function in patients treated with automated peritoneal dialysis. Perit Dial Int,2006,26(3):405-407.
[102]Finkelstein F, Healy H,Abu-Alfa A, et al. Superiority of icodextrin compared with 4.25%dextrose for peritoneal ultraltration[J].J Am Soc Nephrol,2005,16:546-554.
[103]Kim CD, Kwon HM, Park SH, et al. Effects of low glucose degradation products peritoneal dialysis fluid on the peritoneal fibrosis and vascularization in a chronic rat model[J]. Ther Apher Dial,2007,11:56-64.
[104]W illiams JD, TopleyN, CraigKJ, eta.1 TheEuro-Balance tria:1 the effect of a new biocompatible peritoneal dialysis fluid (balance) on the peritoneal membrane[J]. Kidney Int,2004,66(1):408-418
[105]Bazzato G, et al.Lancet,1995 Sep 16;346:740^742
[106]Duman S, Gunal AI, Sen S, Asci G, et al. Does enalanpril prevent peritoneal fibrosis induced by hypertonie(3.86% )peritoneal dialysis solution?Petit Dial Int,2001,21(2),219-224
[107]Hewitson ID, Martic M, Kelynack KJ, et al. Pentoxifytline reduces in vitro renal myofibroblast proliferation and collagen secretion. Am JNephrol, 2000, (1),82-88
[108]FangCC, YenCJ, ChenYM, etal. Pontoxifytline inhibits human peritoneal mesothelial cell growth and collagen synthesis:effects on TGF-beta. Kidney Int,2000,57(6),2626-2630
[109]Hung KY, Huang JW, Chen CT, etal. PontoxifyUine modulates intracellular signalling of TGF-beta in cultured human peritoneal mesothelial cells: implications for prevention of encapsulating peritoneal lsclerosis. Nephrol Dial Transplant,2003,18(4),670-676
[110]姜惠芳,余学清,姜宗培.己酮可可碱对TGF-β1诱导的腹膜间皮细胞胶原ImRNA的表达及细胞外信号调节激酶活性的影响.中山大学学报,2005,26(3);264-267
[111]龚燕梅,姜燕等.己酮可可碱对腹膜纤维化形成的干预作用.华中科技大学学报,2008,37(5);592-594
[112]Hung KY, Chen CT, Huang JW, et al. Dipyridamole inhibits TGF-beta induced。 collagen gene expression in human peritoneal mesothelial cells. Kidney Int, 2001,60(4),1249-1257
[113]CampeseVM, ParkJ. HMG-CoA reductase inhibitors and the kidney[J]. Kidney Int,2007,71:1215-1222.
[114]RUPE REZ M, RODRIGUES-DI EZ R, BLANCO COLIO LM, etal.HMG-CoA reductase inhibitors decrease angiotensin Ⅱ-induced vascular fibrosis:role of RhoA/Rock and MAPKpath-ways[J]. Hypertension,2007,50:377-383.
[115]Haslinger B, KleemannR, Toet KH, etal. Simvastatin suppresses tissue factor expression and increases fibtinolytic activity in tumor necrosis factor-alpha-activated human peritoneal mesothelial cells. Kidney Int,2003, 63:2065-2074.
[116]管红斌,练建红,彭忠兴.等,辛伐他汀抑制腹膜透析相关性腹膜纤维化的实验研究.中国现代医学杂志,2010,20(12):1769-1772
[117]钱敏,何劲松,印荻.辛伐他汀对高糖诱导后人腹膜间皮细胞血管内皮生长因子表达的影响.中国生物化学杂志.2009,30(3):165-167
[118]Turkeapar N, Bayar S, Koyuncu A, et al. Octreotide inhibits hepatic fibrosis, bile duct proliferation and bacterial translocation in obstructive jaundice Hepatongastroenterology,2003,50(51),680-683
[119]Wang ZR, Li DG;, Chen XM, et al. Therapentic efects of octreotide on hepatofibrosis-induced with tetrachloride in rats. Zhonghua Can Zang Bing Za Zhi,2003,11(7),408-411
[120]GunalAI, DumanS, SenS, etal. By reducing TGF beta 1, octrcetide lessens the peritoneal derangements induced by a high glucose solution. J Neprol, 2001,14(3),184-189
[121]GUNAL A I.CELIKER H, AKPOLAT N, et al.By reducing production of vascular endothelial growth factor octreotide improves the peritoneal vascular alteralations induced by hypertonic peritoneal dialysis solution[J]. Perit Dial Int,2002,22(1):301-306
[122]Okuno M, Kojima S, Akita K, et al. Retinoids in liver fibrosis and cancer. Front Biosci,2002;7(1):204-218.
[123]Oseto S, Moriyama T,Kawada N, et al.Therapeutic effect of all-trans retinoic acid on rats with anti-GBM antibody glomerulonephritis. Kidney Int,2003;64(4):1241-1252.
[124]陈惠平,张余光,张涤生.创伤后瘢痕的临床评估及综合治疗.整形再造外科杂志,2004:1(2):113-117.
[125]王桂花,唐晓红,马亚丽.四川大学学报.全反式维甲酸对大鼠腹膜透析模型腹膜TGF-β 1和COL-I表达的影响.2008:39(4):575-578.
[126]Hoff CM, Shockley TR. The potential of gene therapy in the peritoneal cavity[J]. Perit Dial Int,1999,19 (Suppl.2), S202-S207
[127]MargettsPJ, Gyorf fy S, KolbM, etal. Antiangiogenic and antifibrotic gene therapy in a chronic infusion model of peritoneal dialysis in rats[J]. J Am Soc Nephrol,2002,13(3):721-728.
[128]Hekking LH, Harvey VS, Havenith CE,et al. Mesothelial cell transplantation in models of acute inflammation and chronic peritoneal dialysis[J]. Perit Dial Int,2003,23(4):323-330.
[129]何泽云,贺林,李晓峰,等.参麦注射液对大鼠腹膜透析模型腹膜转运功能的影响.湖南中医学院学报,2003,23(2):1-3.
[130]舒静,王怡,张晓云.黄芪注射液拮抗高糖腹膜透析液对腹膜间皮细胞紧密连接的影响.上海中医药大学学报,2007,21(4):51-53
[131]徐海红,张苗,蒋春明.黄芪注射液对腹膜透析相关腹膜间皮细胞TGF-β 1分 泌与表达的影响,中国临床药理学与治疗学,2005,10(7):791-794
[132]张苗,蒋春明.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
[133]刘映红,刘伏友,段绍斌.等.黄芪对TGF-β1致人腹膜间皮细胞分泌腹膜间皮下细胞外基质的影响[J].湖南医科大学学报、2003,28(2):141-4
[134]何劲松,印荻,朱桂松.川芎嗪对高糖诱导后人腹膜间皮细胞血管内皮生长因子表达的影响.中国生化药物杂志,2008,29(6):382-384.
[135]朱桂松,何劲松.川芎嗪注射液对高糖诱导后人腹膜间皮细胞Ⅰ型胶原、金属蛋白酶-1和金属蛋白酶组织抑制剂-1表达的影响.中西医结合学报,2009,7(1):65-69.
[136]朱桂松,何劲松.川芎嗪对高糖诱导后人腹膜间皮转化生长因子-β 1和结缔组织生长因子表达的影响.上海医学,2009,32(3):252-254.
[137]曹东维,张苗,蒋春明.腹透液相关浓度葡萄糖对人腹膜间皮细胞周期蛋白的影响及葛根素的拮抗作用.徐州医学院学报,2008,28(12):787-789.
[138]姜燕,龚燕梅,曾红兵.苦参碱对实验性大鼠腹膜纤维化的影响.中国医院药学杂志,2008,28(24):21 10-2112.
[139]GunalAI, DumanS, SenS, etal. By reducing TGF beta 1, oetrcefide lessens the peritoneal derangements induced by a high glucose solution. J Nephrol 2001,14(3),184-189
[140]蒋春明,陶娜娜,孙(?)等.丹参酮ⅡA对腹膜透析液诱导的大鼠腹膜组织学变化及TGF-β 1表达的影响,东南大学学报,2010,29(4):445-449.
[141]张苗,陶娜娜,蒋春明等.丹参酮ⅡA对腹膜透析液诱导的大鼠腹膜组织学及氧化应激变化的影响,药物生物技术,2010,17(5):412-416.
[142]徐奕,张浩,季迎等.丹参素对高糖刺激腹膜间皮细胞合成细胞外基质的影响,中国中西医结合肾病杂志,2010,11(3):236-237.
[143]席春生,周清发,刘静,等.丹参黄芪对实验大鼠腹膜透析效能及腹膜超微结构的急性影响[J].中国现代医学杂志,2001,11(1):1-3
[144]朱士彦,甘平,曹院国等.苦参碱对高糖致大鼠腹膜间皮细胞NF-κ β p65表达的影响,临床军医杂志,2010,38(5):689-691.
[145]阳晓,叶任高,杨琼琼,等.川芎嗪对大鼠腹膜透析模型腹膜形态和功能的影响[J].中国中西医结合急救杂志,2003,10(2):70-74
[146]阳晓,叶任高,杨琼琼,等.川芎嗪对腹膜间皮细胞CD40表达的影响[J].中国中西医结合杂志,2001,21(12):913-916
[147]赵天然.川芎嗪注射液对腹膜透析的影响.河北中医,2007,29(7):638-639
[148]孙峥,张苗,蒋春明.腹膜透析液中添加黄芪对透析效能的影响.江苏医药,2005,31(4):258-260.
[149]盛梅笑,孙伟,江燕.含黄芪腹透液对高腹膜转运CAPD患者超滤功能的影响.中国中西医结合肾病杂志,2007,8(4):205-207.
[150]蒋春明,张苗,孙.腹膜透析液中添加黄芪对腹腔巨噬细胞功能的影响.医学研究生学报,2005,18(2):135-138.
[151]张苗,孙,蒋春明.葛根素对腹膜透析伴发氧化应激的干预作用.东南大学学报(医学版),2008,27(6):421-424.
[152]李继承,杨则然,张凯.当归、丹参和川芎嗪注射液对腹膜透析液腹腔巨噬细胞功能的干预作用.中国中西医结合杂志,2002,22(3):164-166.
[153]王永钧,张敏鸥.痰瘀互结与肾内微型癥积[J].中国中西医结合肾病杂志,2003,4(1):1-3.
[154]于秀辰,吕仁和.糖尿病肾病的中西医结合治疗[J].中国医刊,2000,35(8):42-43.
[155]孙建芝,牛晓亚,韩丽华等.痰浊证微观辨证指标的实验研究[J].河南中医,1996,16(2):21-22
[156]孙敬昌.从痰瘀论治肾小球硬化理论探析[J].中华中医药学刊,2007,25(8):1691-1693.
[157]方永奇,黄可儿,李小兵.痰证的血液循环特征初探[J].湖北中医杂志,1992,14(6):33-34.
[158]余先杰,吴晋湘,王新星,等.川芎嗪对血管平滑肌细胞增殖的抑制作用及其机理[J].湖南医科大学学报,1992,17(4):350
[159]陈学忠,孙文勇,叶望云,等.川芎嗪、丹参对体外培养成纤维细胞的作用[J].中西医结合杂志,1987,7(9):547
[160]孙林,易著文,虞佩兰.川芎嗪对人胚肾系膜细胞增殖的影响及其机理探讨[J].中国中西医结合杂志,1995,15(3):134
[161]曾升民,魏民,黄启福.川芎嗪及活血注射液对家兔实验性肾小球肾炎的影响[J].中西医结合杂志,1983,3(6):357
[162]屈燧林,方勤,陈高翔,等.汉防已甲素,川芎嗪对苦杏仁苷对人肾成纤维细胞的影响[J].中华肾脏病杂志,2000,16(3):186-189.
[163]秦建华,陈明.大黄素抗肾间质纤维化研究进展[J].中国中西医结合肾病杂志,2006,7(3):184-186.
[164]罗海清,梁东,刘华锋.肾间质纤维化的形成机制及中药防治作用[J].中国中西医结合肾病杂志,2004,5(7):432-434
[165]宁英远,王俭勤.大黄素对人肾成纤维细胞增殖的影响[J].中国中西医结合杂志,2000,20(2):105-106.
[166]王晓玲,王检勤.大黄素对人肾成纤维细胞抑制作用的研究[J]中国中西医结 合肾病杂志,2002,3(11):629.
[167]陈高翔,屈燧林,方勤.大黄素对人胚肾成纤维细胞产生纤溶酶原激活物抑制剂的影响.交通医学,2000,14(6):576-578.
[168]姚建,黎磊石,周红.大黄素对培养人系膜细胞纤维连接蛋白产生的抑制作用.肾脏病与透析肾移植杂志,1994,3(5):349-351.
[169]HuZ, WangZH, PengT, etal. Reno protect effect of fucoidanonadriamycin-in duced glomerulosclerosisinrats[J]. Journal of Shandong University(Health S ciences),2006,44(3):291-295.
[170]Coothan KV, Anthony J, Sreenivasan PP,et al. Renal peroxidative changesmediated by oxalate:the protective role of fucoidan[J]. Life Sciences, 2006,79(19):1789-1795.
[171]刘丽秋,岳少媛,赵秀珍.冬虫夏草对肾小球硬化大鼠肾脏组织抑制因子~1,2mRMN表达的影响[J].肾脏病与透析肾移植杂志,2004,13(5):457-458.[172]张永,丁国华,张建鄂.绞股蓝总皂甙对梗阻性肾病大鼠TGF-β/Smad信号通路及CTGF表达的影响[J].中国医师杂志,2006,8(1):67-69.
[173]Yung et al. Kidney Int,1996:50:1337~1343
[174]Lipkin GW, etal.Nephrol Dial Transplant,1993,8:357~360
[175]Yung SS.etal.Kindney Int,1994,46:527~533
[176]Szeto cc, Chow KM, Lam cw, etal. Clinical bioccompatibility of a neutral peritoneal dialysis solution with minimal glucosedegradation products-A 1-year randomized contriol trial[J]. Nephrol Dial Transplant,2007,22(2): 552-559.
[177]Rastaldi MP,Ferraio F,Giardinol, etal. Epithelial-mesen-chymal transition of tubulan epithelial cells in human renal biopsies[J]. Kidney Int,2002,62 (3):137-146.
[178]史跃先,黎磊石,周虹,等·107例IgA肾病患者肾组织胶原蛋白Ⅳ与肾脏病理关系·解放军医学杂志,1993:18(2):114~117
[179]胡兴荣,崔显念,徐早先.糖尿病肾病HA、 LN、 PCⅢ、 IV-C检测及其临床意义、检验医学与临床,2007,4(3):168-169
[180]孙元莹,李志军,史晓峰,等.益肾康对糖尿病大鼠转化生长因子β1表达的影响.中国中西医结合急救杂志,2004,11(3):169-172
[181]科学技术部.《关于善待实验动物的指导性意见》.2006年9月30日
[182]窦献蕊,余学清,王文健,等.一种新的大鼠慢性腹膜纤维化动物模型的建立.中华肾脏病杂志.2004.12(6):446-449.
[183]项协隆,林沁.腹膜纤维化大鼠模型研究进展[J].医学综
述,2010,16(10):1445-1447.
[184]MargettsPJ, KolbM, Yu L, et al.A chronic inflammatory infusion model of peritoneal dialysis in rats[J]. Perit Dial Int,2001,21(Supp13):368-372.
[185]Nakamoto H, Imai H, Ishida Y, etal. New animal models forencapsulating peritoneal sclerosis-role of acidic solution[J]. Perit Dial Int,2001,21 (Suppl3):S349-353.
[186]GuoH, Leung JC, Lam MF, etal. Smad transgene attenuates peritoneal f ibrosis in uremic rats treated with peritoneal dialysis[J]. JAm Soc Nephro,1 2007,18(10):2689-2703.
[187]MargettsPJ, Kolb M, Galt T, et al. Gene transfer of transforming growth factor-betal to the rat peritoneum:effects on membrane function [J]. JAm Soc Nephro,1 2001,12(10):2029-2039.
[188]Margetts PJ, Bonniaud P, Liu L, et al. Transient overexpression of T GF-{beta}1 induces epithelial mesenchymal transition in the rodentperiton eum[J].JAm Soc Nephro,1 2005,16(2):425-436.
[189]ZareieM, KeuningED, terWee PM, etal. Peritonealdialysis fluid induced changes of the peritoneal membrane are reversible after peritoneal rest in rats[J].Nephrol Dial Transplant,2005,20(1):189-193.
[190]郭群英,叶任高,汪涛,等,透明质酸在大鼠慢性腹膜透析模型中的作用[J].中国病理生理杂志,2001,17(9):834-8390
[191]刘思明,叶任高,汪涛,等.一种简单的慢性腹膜透析高通透性大鼠模型[J].中国病理生理杂志,2001,17(2):186.189
[192]窦献蕊,余学清,郝文科等.TGF-β/Smad信号蛋白在腹膜纤维化腹膜组织上的表达及可能作用.中华医学杂志.20o5.85:2613-2618.
[193]Liu Y. Epithelial to mesenchymal transition in renal fibrogenesis: Pathologic significance, molecular mechanism, and therapeutic interventi on[J]. J Am Soc Nephrol,2004,15(1):1-12
[194]Li J H, Zhu H J, Huang X R, et al. Smad7 inhibits fibrotic effect of TGF-Beta on renal tubular epithelial cells by blocking Smad2 activation [J].J Am Soc Nephrol,2002,13:1464-1472.
[195]Nie J, Dou X, Hao W, et al. Smad7 gene transfer inhibits peritoneal f ibrosis[J]. Kidney Int,2007,72:1336-1344.
[196]Huang YJ, Wang ZH, Zhang JB, et al. Smad7 instead of Smad6 blocks epithelial mesenchymal transition induced by TGF-beta in human renal proximal tubule epithelial cells. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi,2008,24(11):1074-1078.