CNP-NPR-B-cGMP信号通路在肾缺血再灌注损伤中的作用
|
摘要
肾缺血再灌注损伤(ischemia reperfusion injury, IRI)是肾组织缺血时和其后恢复血液灌注时器官功能不能恢复正常,甚至发生更为严重的组织损伤或器官功能衰竭。肾脏由于其组织结构和功能的特殊性,对缺血再灌注损伤特别敏感,临床上常见因缺血引起急性肾功能衰竭(acute renal failue, ARF)的发生,如急性缺血性肾功衰竭、心肺复苏、心脏体外循环、失血性休克、严重脱水、弥散性血管内凝血、心脏手术及肾脏移植术等过程中,特别是多器官功能衰竭的危重患者几乎都伴有ARF的发生。尽管进行积极的对症支持治疗,但还是出现很高的发病率和死亡率。实验证明,心房钠尿肽(atrial natriuretic peptide, ANP)可有效地减轻心脏、肝脏及胃等器官的缺血再灌注损伤,起明显的保护作用。近年来研究表明,ANP对大鼠肾缺血再灌注损伤也具有保护作用,其保护作用是增加肾小球滤过率(glomerular filtration rate, GFR)和肾髓质的血流量,减轻髓质部生成表皮生长因子(epithelial growth factor, EGF)细胞的损伤,恢复肾小管上皮细胞的完整性；ANP可减轻中性白细胞的活性,抑制其释放各种炎症介质和氧自由基的生成保护肾功能,但其作用机制尚不清楚。
钠尿肽(natriuretic peptides, NPs)是新发现的肽类激素,主要有ANP、脑钠尿肽(brain natriuretic peptide, BNP)及C-型钠尿肽(C-type natriuretic peptide,CNP)等,其共有的效应是利尿、排钠、舒张血管、降低血压和调节水电解质平衡。ANP和BNP主要由心脏合成和分泌,而CNP主要由内皮细胞分泌,是脑或神经系统特异性表达的神经递质。现已确认能与钠尿肽结合的受体有三种亚型：A型钠尿肽受体(natriuretic peptide receptor type A, NPR-A)、B型钠尿肽受体(natriuretic peptide receptor type B, NPR-B)及清除型钠尿肽受体(natriuretic peptide clearance receptor, NPR-C)。ANP和BNP主要与NPR-A结合,CNP则主要与NPR-B结合而发挥其生物学效应。研究表明,钠尿肽及其受体广泛分布在肾脏,但是NPs-NPR-cGMP系统在肾缺血再灌注的病理生理学作用尚不甚清楚。
为此,本研究从形态学和分子生物学等角度观察和探讨CNP-NPR-B-cGMP信号通路在肾缺血再灌注损伤中的作用及其机制。
本研究利用大鼠肾缺血再灌注模型,制备血清样本测定肌酐(creatinine, Cr)、尿素氮(blood urine nitrogen, BUN)等肾功能指标,且利用光镜和电镜观察肾组织形态学及肾组织超微结构,利用放射免疫分析和酶联免疫法测定血清CNP浓度,采用RT-PCR和免疫组织化学方法观察CNP及NPR-B mRNA的表达和分布。另外,取24只SD大鼠随机分为假手术组(sham)、肾缺血再灌注组(ischemia reperfusion, IR)及肾缺血再灌注即时CNP给药组(IR+CNP)(每组8只),测定血清Cr、BUN及肾组织SOD活性及MDA含量,且利用光镜观察肾组织形态学变化和采用免疫印迹技术观察肾组织Bax、Bcl-2的表达变化。
实验结果如下：
1.大鼠肾缺血再灌注组血清Cr、BUN水平且明显高于假手术组(n=8,P<0.01),并呈现时间依赖性特征。
2.假手术组肾脏组织结构清楚,肾小管上皮细胞完整,只有轻度炎性细胞浸润；IR组肉眼观察可见肾脏体积明显增大而质软,剖面见肾髓质呈暗红色；皮质肿胀而苍白。显微镜下观察,IR组近端肾小管上皮细胞空泡及颗粒变性,细胞扁平,管腔扩张,刷状缘脱落消失,管腔内有脱落的上皮、管型和炎症渗出物；基底膜裸露,甚至呈现肾小管细胞的节段性灶状坏死。肾小管间质有不同程度的炎症细胞浸润和水肿。远端肾小管和集合管管腔内可见细胞碎片或颗粒管型,肾小管基底膜节段性断裂,断裂部位可见淋巴细胞、单核细胞及中性粒细胞浸润,肾间质弥漫并水肿。sham组电镜下超微结构基本正常,线粒体嵴完整,未见肿胀,粗面内质网结构完整,排列整齐；IR组电镜下可见肾小管上皮细胞微绒毛脱落,线粒体肿胀、线粒体嵴消失,内质网扩张,初级和次级溶酶体增多,吞噬空胞亦可见有增多现象。甚至上皮细胞崩解脱落,仅可见裸露或断裂的基底膜。
3.假手术组及缺血再灌注组不同时间段(0/1/2/4h)血清CNP含量无明显差异(n=8,P>0.05)。
4.缺血再灌注组肾组织CNP mRNA表达明显上调,且在再灌注2 hour时表达最高(n=8,P<0.05)。
5.假手术组及缺血再灌注组肾组织NPR-B均呈阳性,可见到散在分布的棕色颗粒,但与假手术组相比再灌注组呈阳性的棕色颗粒明显增多,染色明显加深。另外,缺血再灌注组大鼠肾组织中NPR-B mRNA表达明显高于正常对照组。
6.假手术组肾脏组织结构清楚,肾小管上皮细胞完整,只有轻度炎性细胞浸润；再灌注组肾脏体积明显增大而质软,剖面见肾髓质呈暗红色；皮质肿胀而苍白。显微镜下近端肾小管上皮细胞空泡及颗粒变性,细胞扁平,管腔扩张,刷状缘脱落消失,管腔内有脱落的上皮、管型和炎症渗出物,基底膜裸露,甚至可见肾小管细胞的节段性灶状坏死。肾小管间质可有不同程度的炎症细胞浸润和水肿,远端肾小管和集合管管腔内可见细胞碎片或颗粒管型。肾小管基底膜节段性断裂,断裂部位可见淋巴细胞、单核细胞及中性粒细胞浸润,肾间质弥漫水肿。肾小球和肾小动脉未见明显改变。CNP组肾小管排列基本正常,以肿胀为主,肾间质水肿、充血,炎性细胞浸润不明显。
7.缺血再灌注组24小时后血清Cr、BUN水平明显高于假手术组(n=8,P<0.001);CNP即时给药组较缺血再灌注组明显下降(n=8,P<0.05)。
8.缺血再灌注组与假手术组相比MDA含量显著升高,SOD活性显著下降(n=8,P<0.01和P<0.05)；CNP即时给药组与IR组相比MDA含量明显减少,SOD活性有所提高(n=8,P<0.01和P<0.05)。
9.与假手术组及CNP即时给药组相比,缺血再灌注组肾组织Bax表达明显增加(n=8,P<0.05),而Bcl-2的表达在3组之间无明显差异,但是CNP即时给药组Bax/Bcl-2比值降低(n=8,P<0.05)。
以上结果提示：
1.肾缺血再灌注时组织结构和功能明显受到损伤,尤其在皮髓交界区和髓质部位。
2.肾缺血再灌注损伤时肾组织CNP及NPR-B的表达明显上调。
3.CNP明显改善缺血再灌注损伤的肾脏组织结构和功能,呈现抗损伤作用。
4.CNP对损伤的肾组织具有明显的抗氧化作用。
5.CNP对缺血再灌注肾具有明显的抗细胞凋亡效应,其作用是通过上调抗凋亡基因表达的途径实现的。
Ischemia reperfusion (IR) may caused renal structural and functional injury in kidney. Because of the renal particularity of structure and function, kidney was showed especially sensitive for ischemia reperfusion injury (IRI). Therefore, there were common renal diseases in clinical patients such as acute renal failure (ARF) and showed high morbidity and mortality in patients. Experimental data demonstrated that atrial natriuretic peptide (ANP)may reduced reperfusion injuries of the heart, liver, and the stomach etc and showed evident protective effcts in human and several animals. Is was also demonstrated that ANP may had protective function in IRI rat kidney via increase renal glomerular filtration rate, blood flow in medullar and reduce of epithelial cells injury in renal medullar and therefore recuperates integrality of dubular epithelial cells. On the other hand, ANP my reduces neutrophilic activity, inhibits secreiton of mediators of inflammations and reduces production of reactive oxygen species. However, the mechanism of ANP on ischemia reperfusion injury especially for ARF is not well kown.
Natriuretic peptides (NPs), as a family of hormen, thare are four members in NPs I. E. ANP, brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP). NPs may induce diuresis, sodium excretion, vessel dilatation, blood pressure regulation and electrolyte balance. The heart sythesis and release of ANP and BNP. CNP is sythesised by endothelial cells and play paracrine function in serise of tissues, such as the heart, vessel, nervous system etc. There are three types of the NP receptors (NPRs), NPR-A, NPR-B and NPR-C (NP clearance receptor). ANP and BNP mainly bingding to NPR-A and CNP maily bingding to NPR-B. Several experiments indicate that NPs and NPRs distributed in kidney but effects of NPs-cGMP on renal ischemia reperfusion injury are not clear. Therefor, the purpose of the precent is to investigate the effect of CNP-NPR-B-cGMP signaling pathway on renal ischemia reperfusion injury by using rat renal ischemia reperfusion model. immunohistochemistry methods, RT-PCR, ELISA etc. The renal structural changes are observed by microscope. Renal superoxide dismutase (SOD) activities, malondialdehyde (MDA) levels, Bax and Bcl-2 gene expressions are also to detected. In addition, creatinine (Cr) and blood urine nitrogen (BUN) levels are measured by autobiochemicaldetector. On the other hand, the rats will be randomly divided into three groups:sham operration group(sham), IR group(IR)and IR+CNP group (IR+CNP) (n=8 in each groups).
The results of the precent experiments as follows:
1. Levels of Cr and BUN were increaseed by time-dependent manna after renal ischemia reperfusion (n=8, P<0.01 vs sham goup).
2. In sham group, renal organization was clearly and epithelial cells of tubules were completed, only a minor inflammatory cells were observed. In IR group, under microscope can be seen near the end of the epithelial cells from an empty bubble and particles of tunica adventitia. The flat, the paint off, or fate, the detachment of the epithelial cells, inflammatory exudate. The basement membrane is bare. Glomerular and kidney arterioles not change. sham group the structure of under electronic microscope is normal, mitochondria integrity, not swell, rough endoplasmic reticulum structural integrity; and IR group the nephridial tube epithelial cells microvilli off, mitochondria turgescence, mitochondria and endoplasmic abnormal reticulum distention, primary and secondary mixed up in a body and empty cell can also see that there is increasing. even the epithelial cells from collapse, and only thus is bare or break the substrate.
3. The levels of CNP were unchanged in sham and IR groups (n=8, P>0.05 vs sham group).
4. Expression of CNP mRNA were increased in IR group rats and showed time-dependent manna (n=8, P<0.05). The peake of CNP mRNA expression were observed at 2 houres after perfused in rats.
5. In sham group, immunohistochemical data demonstrated that NPR-B were distributed widly in kidney. In IR group, renal NPR-B were increased compared with sham group significiently. RT-PCR data of NPR-B were similarly about with the immunohistochemical data.
6. After RIR the histological morphologh analysis demonstrated phathologic change significantly. The electron microscope data indicated that IR caused mitochondrial injury and showed obviously swelling, some of the cristae became vacular-like; the microvilli of the Proximal tubule cells were scare and swelled, rough endoplasmic reticulums were reduced in number, foamy changes in the structure of nuclear and cytoplasm were also observed. In CNP group, the microvilli were slightly swelled or kept intact; the cristae of the mitochondria were slightly changed but the structure was still intact; rough endoplasmic reticulums were slightly swelled ribsome was all preserved, nuclear had almost normal figure with very clear nucleolus.
7. Serum levels of Cr and BUN in IR group rats were significantly increased after reperfused for 24 hours (n=8, P<0.001vs sham group), and the serum levels of Cr and BUN were significantly reduced by CNP pretreatment after renal ischemia reperfusion (n=8, P<0.05 vs IR group).
8. In IR group, the MDA contents were increased and SOD activity were significantly reduced after renal reperfusion (n=8, P<0.001and P<0.05 vs sham group). CNP may significantly reduced levels of MDA and slightly increased the activity of SOD after ischemia reperfusion in rat kidney (n=8, P<0.001and P<0.05 vs sham group).
9. Reanal Bax gene expression was increased by ischemia reperfusion injury (n=8, P<0.05 vs sham or IR+CNP groups) without changes of Bcl-2 expression, but the ratio of Bax/Bcl-2 was decreased by CNP treatment in IR+CNP group (n=8, P<0.05 vs IR group).
Thease results indicat that:
1. Ischemia reperfusion my causes renal structural and functional injury especially in renal junctional zone of the cortex and medulla in rat kidney.
2. Renal ischemia reperfusion injury induces up rangulation of CNP and NPR-B mRNA expression in rat kidney.
3. CNP may improves renal structrue and function in ischemia reperfusion injury rat kidney.
4. CNP has been shown antioxidant effect in rat kidney.
5. CNP has been shown antiapoptosis effect in ischemia reperfusion rat kidney via up regulation of Bax/Bcl-2 ratio pathway.
钠尿肽(natriuretic peptides, NPs)是新发现的肽类激素,主要有ANP、脑钠尿肽(brain natriuretic peptide, BNP)及C-型钠尿肽(C-type natriuretic peptide,CNP)等,其共有的效应是利尿、排钠、舒张血管、降低血压和调节水电解质平衡。ANP和BNP主要由心脏合成和分泌,而CNP主要由内皮细胞分泌,是脑或神经系统特异性表达的神经递质。现已确认能与钠尿肽结合的受体有三种亚型：A型钠尿肽受体(natriuretic peptide receptor type A, NPR-A)、B型钠尿肽受体(natriuretic peptide receptor type B, NPR-B)及清除型钠尿肽受体(natriuretic peptide clearance receptor, NPR-C)。ANP和BNP主要与NPR-A结合,CNP则主要与NPR-B结合而发挥其生物学效应。研究表明,钠尿肽及其受体广泛分布在肾脏,但是NPs-NPR-cGMP系统在肾缺血再灌注的病理生理学作用尚不甚清楚。
为此,本研究从形态学和分子生物学等角度观察和探讨CNP-NPR-B-cGMP信号通路在肾缺血再灌注损伤中的作用及其机制。
本研究利用大鼠肾缺血再灌注模型,制备血清样本测定肌酐(creatinine, Cr)、尿素氮(blood urine nitrogen, BUN)等肾功能指标,且利用光镜和电镜观察肾组织形态学及肾组织超微结构,利用放射免疫分析和酶联免疫法测定血清CNP浓度,采用RT-PCR和免疫组织化学方法观察CNP及NPR-B mRNA的表达和分布。另外,取24只SD大鼠随机分为假手术组(sham)、肾缺血再灌注组(ischemia reperfusion, IR)及肾缺血再灌注即时CNP给药组(IR+CNP)(每组8只),测定血清Cr、BUN及肾组织SOD活性及MDA含量,且利用光镜观察肾组织形态学变化和采用免疫印迹技术观察肾组织Bax、Bcl-2的表达变化。
实验结果如下：
1.大鼠肾缺血再灌注组血清Cr、BUN水平且明显高于假手术组(n=8,P<0.01),并呈现时间依赖性特征。
2.假手术组肾脏组织结构清楚,肾小管上皮细胞完整,只有轻度炎性细胞浸润；IR组肉眼观察可见肾脏体积明显增大而质软,剖面见肾髓质呈暗红色；皮质肿胀而苍白。显微镜下观察,IR组近端肾小管上皮细胞空泡及颗粒变性,细胞扁平,管腔扩张,刷状缘脱落消失,管腔内有脱落的上皮、管型和炎症渗出物；基底膜裸露,甚至呈现肾小管细胞的节段性灶状坏死。肾小管间质有不同程度的炎症细胞浸润和水肿。远端肾小管和集合管管腔内可见细胞碎片或颗粒管型,肾小管基底膜节段性断裂,断裂部位可见淋巴细胞、单核细胞及中性粒细胞浸润,肾间质弥漫并水肿。sham组电镜下超微结构基本正常,线粒体嵴完整,未见肿胀,粗面内质网结构完整,排列整齐；IR组电镜下可见肾小管上皮细胞微绒毛脱落,线粒体肿胀、线粒体嵴消失,内质网扩张,初级和次级溶酶体增多,吞噬空胞亦可见有增多现象。甚至上皮细胞崩解脱落,仅可见裸露或断裂的基底膜。
3.假手术组及缺血再灌注组不同时间段(0/1/2/4h)血清CNP含量无明显差异(n=8,P>0.05)。
4.缺血再灌注组肾组织CNP mRNA表达明显上调,且在再灌注2 hour时表达最高(n=8,P<0.05)。
5.假手术组及缺血再灌注组肾组织NPR-B均呈阳性,可见到散在分布的棕色颗粒,但与假手术组相比再灌注组呈阳性的棕色颗粒明显增多,染色明显加深。另外,缺血再灌注组大鼠肾组织中NPR-B mRNA表达明显高于正常对照组。
6.假手术组肾脏组织结构清楚,肾小管上皮细胞完整,只有轻度炎性细胞浸润；再灌注组肾脏体积明显增大而质软,剖面见肾髓质呈暗红色；皮质肿胀而苍白。显微镜下近端肾小管上皮细胞空泡及颗粒变性,细胞扁平,管腔扩张,刷状缘脱落消失,管腔内有脱落的上皮、管型和炎症渗出物,基底膜裸露,甚至可见肾小管细胞的节段性灶状坏死。肾小管间质可有不同程度的炎症细胞浸润和水肿,远端肾小管和集合管管腔内可见细胞碎片或颗粒管型。肾小管基底膜节段性断裂,断裂部位可见淋巴细胞、单核细胞及中性粒细胞浸润,肾间质弥漫水肿。肾小球和肾小动脉未见明显改变。CNP组肾小管排列基本正常,以肿胀为主,肾间质水肿、充血,炎性细胞浸润不明显。
7.缺血再灌注组24小时后血清Cr、BUN水平明显高于假手术组(n=8,P<0.001);CNP即时给药组较缺血再灌注组明显下降(n=8,P<0.05)。
8.缺血再灌注组与假手术组相比MDA含量显著升高,SOD活性显著下降(n=8,P<0.01和P<0.05)；CNP即时给药组与IR组相比MDA含量明显减少,SOD活性有所提高(n=8,P<0.01和P<0.05)。
9.与假手术组及CNP即时给药组相比,缺血再灌注组肾组织Bax表达明显增加(n=8,P<0.05),而Bcl-2的表达在3组之间无明显差异,但是CNP即时给药组Bax/Bcl-2比值降低(n=8,P<0.05)。
以上结果提示：
1.肾缺血再灌注时组织结构和功能明显受到损伤,尤其在皮髓交界区和髓质部位。
2.肾缺血再灌注损伤时肾组织CNP及NPR-B的表达明显上调。
3.CNP明显改善缺血再灌注损伤的肾脏组织结构和功能,呈现抗损伤作用。
4.CNP对损伤的肾组织具有明显的抗氧化作用。
5.CNP对缺血再灌注肾具有明显的抗细胞凋亡效应,其作用是通过上调抗凋亡基因表达的途径实现的。
Ischemia reperfusion (IR) may caused renal structural and functional injury in kidney. Because of the renal particularity of structure and function, kidney was showed especially sensitive for ischemia reperfusion injury (IRI). Therefore, there were common renal diseases in clinical patients such as acute renal failure (ARF) and showed high morbidity and mortality in patients. Experimental data demonstrated that atrial natriuretic peptide (ANP)may reduced reperfusion injuries of the heart, liver, and the stomach etc and showed evident protective effcts in human and several animals. Is was also demonstrated that ANP may had protective function in IRI rat kidney via increase renal glomerular filtration rate, blood flow in medullar and reduce of epithelial cells injury in renal medullar and therefore recuperates integrality of dubular epithelial cells. On the other hand, ANP my reduces neutrophilic activity, inhibits secreiton of mediators of inflammations and reduces production of reactive oxygen species. However, the mechanism of ANP on ischemia reperfusion injury especially for ARF is not well kown.
Natriuretic peptides (NPs), as a family of hormen, thare are four members in NPs I. E. ANP, brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP). NPs may induce diuresis, sodium excretion, vessel dilatation, blood pressure regulation and electrolyte balance. The heart sythesis and release of ANP and BNP. CNP is sythesised by endothelial cells and play paracrine function in serise of tissues, such as the heart, vessel, nervous system etc. There are three types of the NP receptors (NPRs), NPR-A, NPR-B and NPR-C (NP clearance receptor). ANP and BNP mainly bingding to NPR-A and CNP maily bingding to NPR-B. Several experiments indicate that NPs and NPRs distributed in kidney but effects of NPs-cGMP on renal ischemia reperfusion injury are not clear. Therefor, the purpose of the precent is to investigate the effect of CNP-NPR-B-cGMP signaling pathway on renal ischemia reperfusion injury by using rat renal ischemia reperfusion model. immunohistochemistry methods, RT-PCR, ELISA etc. The renal structural changes are observed by microscope. Renal superoxide dismutase (SOD) activities, malondialdehyde (MDA) levels, Bax and Bcl-2 gene expressions are also to detected. In addition, creatinine (Cr) and blood urine nitrogen (BUN) levels are measured by autobiochemicaldetector. On the other hand, the rats will be randomly divided into three groups:sham operration group(sham), IR group(IR)and IR+CNP group (IR+CNP) (n=8 in each groups).
The results of the precent experiments as follows:
1. Levels of Cr and BUN were increaseed by time-dependent manna after renal ischemia reperfusion (n=8, P<0.01 vs sham goup).
2. In sham group, renal organization was clearly and epithelial cells of tubules were completed, only a minor inflammatory cells were observed. In IR group, under microscope can be seen near the end of the epithelial cells from an empty bubble and particles of tunica adventitia. The flat, the paint off, or fate, the detachment of the epithelial cells, inflammatory exudate. The basement membrane is bare. Glomerular and kidney arterioles not change. sham group the structure of under electronic microscope is normal, mitochondria integrity, not swell, rough endoplasmic reticulum structural integrity; and IR group the nephridial tube epithelial cells microvilli off, mitochondria turgescence, mitochondria and endoplasmic abnormal reticulum distention, primary and secondary mixed up in a body and empty cell can also see that there is increasing. even the epithelial cells from collapse, and only thus is bare or break the substrate.
3. The levels of CNP were unchanged in sham and IR groups (n=8, P>0.05 vs sham group).
4. Expression of CNP mRNA were increased in IR group rats and showed time-dependent manna (n=8, P<0.05). The peake of CNP mRNA expression were observed at 2 houres after perfused in rats.
5. In sham group, immunohistochemical data demonstrated that NPR-B were distributed widly in kidney. In IR group, renal NPR-B were increased compared with sham group significiently. RT-PCR data of NPR-B were similarly about with the immunohistochemical data.
6. After RIR the histological morphologh analysis demonstrated phathologic change significantly. The electron microscope data indicated that IR caused mitochondrial injury and showed obviously swelling, some of the cristae became vacular-like; the microvilli of the Proximal tubule cells were scare and swelled, rough endoplasmic reticulums were reduced in number, foamy changes in the structure of nuclear and cytoplasm were also observed. In CNP group, the microvilli were slightly swelled or kept intact; the cristae of the mitochondria were slightly changed but the structure was still intact; rough endoplasmic reticulums were slightly swelled ribsome was all preserved, nuclear had almost normal figure with very clear nucleolus.
7. Serum levels of Cr and BUN in IR group rats were significantly increased after reperfused for 24 hours (n=8, P<0.001vs sham group), and the serum levels of Cr and BUN were significantly reduced by CNP pretreatment after renal ischemia reperfusion (n=8, P<0.05 vs IR group).
8. In IR group, the MDA contents were increased and SOD activity were significantly reduced after renal reperfusion (n=8, P<0.001and P<0.05 vs sham group). CNP may significantly reduced levels of MDA and slightly increased the activity of SOD after ischemia reperfusion in rat kidney (n=8, P<0.001and P<0.05 vs sham group).
9. Reanal Bax gene expression was increased by ischemia reperfusion injury (n=8, P<0.05 vs sham or IR+CNP groups) without changes of Bcl-2 expression, but the ratio of Bax/Bcl-2 was decreased by CNP treatment in IR+CNP group (n=8, P<0.05 vs IR group).
Thease results indicat that:
1. Ischemia reperfusion my causes renal structural and functional injury especially in renal junctional zone of the cortex and medulla in rat kidney.
2. Renal ischemia reperfusion injury induces up rangulation of CNP and NPR-B mRNA expression in rat kidney.
3. CNP may improves renal structrue and function in ischemia reperfusion injury rat kidney.
4. CNP has been shown antioxidant effect in rat kidney.
5. CNP has been shown antiapoptosis effect in ischemia reperfusion rat kidney via up regulation of Bax/Bcl-2 ratio pathway.
引文
1. Kucuk A, Kabadere S, Tosun M, et al. Protective effects of doxycycline in ischemia/reperfusion injury on kidney. J Physiol Biochem.2009,65(2):183-191.
2. Ramesh G, Reeves WB. Inflammatory cytokines in acute renal failure. Kidney Int Suppl.2004,(91):S56-61.
3. Furuichi K, Wada T, Yokoyama H, et al. Role of Cytokines and Chemokines in Renal Ischemia-Reperfusion Injury. Drug News Perspect.2002,15(8):477-482.
4. Liangos O, Tighiouart H, Perianayagam MC, et al. Comparative analysis of urinary biomarkers for early detection of acute kidney injury following cardiopulmonary bypass. Biomarkers.2009,14(6):423-431.
5. Burne-Taney MJ, Rabb H. The role of adhesion molecules and T cells in ischemic renal injury. Curr OpinNephrol Hypertens.2003,12(1):85-90.
6. Ysebaert DK, De Greef KE, De Beuf A, et al. T cells as mediators in renal ischemia/reperfusion injury. Kidney Int.2004,66(2):491-496.
7. Friedewald JJ, Rabb H. Inflammatory cells in ischemic acute renal failure. Kidney Int. 2004,66(2):486-491.
8. Bonventre JV, Zuk A. Ischemic acute renal failure:an inflammatory disease? Kidney Int.2004,66(2):480-485.
9. Singbartl K, Ley K. Leukocyte recruitment and acute renal failure. J Mol Med.2004, 82(2):91-101.
10. Andreucci M, Michael A, Kramers C, et al. Renal ischemia/reperfusion and ATP depletion/repletion in LLC-PK(1) cells result in phosphorylation of FKHR and FKHRL1. Kidney Int.2003,64(4):1189-1198.
11. Tilney NL, Guttmann RD. Effects of initial ischemia/reperfusion injury on the transplanted kidney. Transplantation.1997,64(7):945-947.
12. Okusa MD. The inflammatory cascade in acute ischemic renal failure. Nephron.2002, 90(2):133-138.
13. Arumugam TV, Shiels IA, Woodruff TM, et al. The role of the complement system in ischemia-reperfusion injury. Shock.2004,21(5):401-409.
14. Yamada K, Miwa T, Liu J, et al. Critical protection from renal ischemia reperfusion injury by CD55 and CD59. J Immunol.2004,172(6):3869-3875.
15. Thurman JM, Ljubanovic D, Edelstein CL, et al. Lack of a functional alternative complement pathway ameliorates ischemic acute renal failure in mice. J Immunol. 2003,170(3):1517-1523.
16. Arumugam TV, Shiels IA, Strachan AJ, et al. A small molecule C5a receptor antagonist protects kidneys from ischemia/reperfusion injury in rats. Kidney Int.2003,63(1): 134-142.
17. di Mari JF, Davis R, Safirstein RL. MAPK activation determines renal epithelial cell survival during oxidative injury. Am J Physiol.1999,277(2 Pt 2):F195-203.
18. De Bold, AJ, Borenstein HB, Veress AT, et al. A rapid and potent natriuretic response to intravenous injection of atrial myocardial extracts in rats. Life Sci.1981,28:89-94.
19. Sudoh T, Kangawa K, Minamino N, et al. A new natriuretic peptide in porcine brain[J]. Nature.1988,322(6159):78-81.
20. Sudoh T, Minamino N, Kangawa W, et al. C-type natriuretic peptide (CNP):A new member of natriuretic peptide family identified in porcine brain[J]. Bichem Biophys Res Commun.1990,168(2):863-870.
21. Schweitz H, Vigne P, Moinier D, et al. A new member of the natriuretic peptide family is present in the venom of the green mamba (Dendroaspis angusticeps) [J]. J Biol Chem.1992,267(20):13928-13932.
22. Cahill PA, Hassid A. Clearance receptor-binding atrial natriuretic peptides inhibit mitogenesis and proliferation of rat aortic smooth muscle cells. Biochem Biophys Res Commun.1991,179(3):1606-1613.
23. Levin ER. Natriuretic peptide C-receptor:more than a clearance receptor. Am J Physiol. 1993,264(4 Pt 1):E483-489.
24. Chujo K, Ueno M, Asaga T, et al. Atrial natriuretic peptide enhances recovery from ischemia/reperfusion-induced renal injury in rats. J Biosci Bioeng.2010,109(6): 526-530.
25. Chujo K, Ueki M, Asaga T, et al. Atrial natriuretic peptide attenuates ischemia/reperfusion-induced renal injury by reducing neutrophil activation in rats. Tohoku J Exp Med.2008,215(3):257-266.
26. Yoshimoto T, Naruse M, Naruse K, et al. Modulation of vascular natriuretic peptide receptor gene expression in hypertensive and obese hyperglycemic rats. Endocrinology.1995,136(6):2427-2434.
27. Kar NL,Josephe KL,Timothy GY. Gene expression and synthesis of natriuretic peptide by cultured human glomular hyperters.1999,17:575-583
28. Lohe A, Yeh I, Hyver T, et al. Natriuretic peptide B receptor and C-type natriuretic peptide in the rat kidney. J Am Soc Nephrol.1995,6(6):1552-1558.
29. Igaki T, Itoh H, Suga S, et al. C-type natriuretic peptide in chronic renal failure and its action in humans. Kidney Int 49.1996,55:S144-S147,
30. Lai FJ, Hsieh MC, Hsin SC,et al. The cellular localization of increased atrial natriuretic peptide mRNA and immunoreactivity in diabetic rat kidneys. J Histochem Cytochem. 2002,50(11):1501-1508.
31. Terada Y, Tomita K, Nonoguchi H, et al. PCR localization of C-type natriuretic peptide and B-type receptor mRNAs in rat nephron segments. Am J Physiol.1994,267(2 Pt 2): F215-222.
32. Suzuki E, Hirata Y, Hayakawa H, et al. Evidence for C-type natriuretic peptide production in the rat kidney. Biochem Biophys Res Commun.1993,192(2):532-538
33. Kar NL,Josephe KL,Timothy GY. Gene expression and synthesis of natriuretic peptide by cultured human glomular hyperters.1999,17:575-583
34. Giilberg V, M(?)ller S, Henriksen JH, et al. Increased renal production of C-type natriuretic peptide (CNP) in patients with cirrhosis and functional renal failure. Gut. 2000,47(6):852-857.
35. Sansoe G, Aragno M, Mastrocola R, et al. Overexpression of kidney neutral endopeptidase (EC 3.4.24.11) and renal function in experimental cirrhosis. Am J Physiol Renal Physiol.2006,290(6):F1337-1343.
36. Chen HH, Burnett JC Jr. C-type natriuretic peptide:the endothelial component of the natriuretic peptide system. J Cardiovasc Pharmacol.1998,3:S22-28.
37. Lohe A, Yeh I, Hyver T, et al. Natriuretic peptide B receptor and C-type natriuretic peptide in the rat kidney. J Am Soc Nephrol.1995,6(6):1552-1558.
38. Datta SR, Brunet A, Greenberg ME. Cellular survival:a play in three Akts. Genes Dev. 1999,13(22):2905-2927.
39. Cross TG, Scheel-Toellner D, Henriquez NV, et al. Serine/threonine protein kinases and apoptosis. Exp Cell Res.2000,256(1):34-41.
40. Andreucci M, Michael A, Kramers C, et al. Renal ischemia/reperfusion and ATP depletion/repletion in LLC-PK(1) cells result in phosphorylation of FKHR and FKHRL1. Kidney Int.2003,64(4):1189-1198.
1. Kucuk A, Kabadere S, Tosun M, et al. Protective effects of doxycycline in ischemia/reperfusion injury on kidney. J Physiol Biochem.2009,65(2):183-191.
2. Ramesh G, Reeves WB. Inflammatory cytokines in acute renal failure. Kidney Int Suppl.2004, (91):S56-61.
3. Furuichi K, Wada T, Yokoyama H, et al. Role of Cytokines and Chemokines in Renal Ischemia-Reperfusion Injury. Drug News Perspect.2002,15(8):477-482.
4. Liangos O, Tighiouart H, Perianayagam MC, et al. Comparative analysis of urinary biomarkers for early detection of acute kidney injury following cardiopulmonary bypass. Biomarkers.2009,14(6):423-431.
5. Chujo K, Ueno M, Asaga T, et al. Atrial natriuretic peptide enhances recovery from ischemia/reperfusion-induced renal injury in rats. J Biosci Bioeng.2010,109(6): 526-530.
6. Chujo K, Ueki M, Asaga T, et al. Atrial natriuretic peptide attenuates ischemia/reperfusion-induced renal injury by reducing neutrophil activation in rats. Tohoku J Exp Med.2008,215(3):257-266.
7. Sudoh T, Minamino N, Kangawa K, et al. C-type natriuretic peptide (CNP):a new member of natriuretic peptide family identified in porcine brain. Biochem Biophys Res Commun.1990,168(2):863-870.
8. Gulberg V, M(?)ller S, Henriksen JH, et al. Increased renal production of C-type natriuretic peptide (CNP) in patients with cirrhosis and functional renal failure. Gut. 2000,47(6):852-857.
9. Igaki T, Itoh H, Suga S, et al. C-type natriuretic peptide in chronic renal failure and its action in humans. Kidney Int 49.1996,55:S144-S147.
10. Holleyman CR, Larson DF. Apoptosis in the ischemic reperfused myocardium. Perfusion.2001,16(6):491-502.
11. Schramm L, Heidbreder E, Lukes M, et al. Endotoxin-induced acute renal failure in the rat:effects of urodilatin and diltiazem on renal function. Clin Nephrol.1996,46(2): 117-124.
12. Spek CA, Bruggemann LW, Borensztajn KS. Protease-activated receptor 2 blocking peptide counteracts endotoxin-induced inflammation and coagulation and ameliorates renal fibrin deposition in a rat model of acute renal failure. Shock.2010,33(3):339.
13. Hengartner MO. The biochemistry of apoptosis. Nature.2000,407(6805):770-776.
14. Thornberry NA, Lazebnik Y. Caspases:enemies within. Science.1998,281(5381): 1312-1316.
15. Kaushal GP, Kaushal V, Hong X,,et al. Role and regulation of activation of caspases in cisplatin-induced injury to renal tubular epithelial cells. Kidney Int.2001,60(5): 1726-1736.
16. Bonegio R, Lieberthal W. Role of apoptosis in the pathogenesis of acute renal failure. Curr Opin Nephrol Hypertens.2002,11(3):301-308.
17. Saikumar P, Venkatachalam MA. Role of apoptosis in hypoxic/ischemic damage in the kidney. Semin Nephrol.2003,23(6):511-521.
18. Eschwege P, Paradis V, Conti M, et al. Bcl-2 and Bax expression on rat ischemic kidney.Transplant Proc.1998,30(6):2861-2862.
19.史明,张文岚,薄立华.肾缺血再灌注细胞内钙水平与氧化应激损伤研究[J].中国生物制品学杂志,2003,16(5)：311-313.
20.傅耀文,张文岚,薛立娟等.缺血再灌注对肾细胞内钙水平与细胞凋亡的影响[J].中华泌尿外科杂志,2004,25(12)：834-837.
21. Chatterjee PK, Brown PA, Cuzzocrea S, et al. Calpain inhibitor-1 reduces renal ischemia/reperfusion injury in the rat. Kidney Int.2001,59(6):2073-2083.
22. Jiang S, Chen Y, Zou J, et al. Diverse effects of ischemic pretreatments on the long-term renal damage induced by ischemia-reperfusion. Am J Nephrol.2009,30(5): 440-449.
1. De Bold, AJ, Borenstein HB, et al. Sonnenberg H. A rapid and potent natriuretic response to intravenous injection of atrial myocardial extracts in rats[J]. Life Sci,1981, 28(1):89-94.
2. Sudoh T, Kangawa K, Minamino N, et al. A new natriuretic peptide in porcine brain[J]. Nature,1988,322(6159):78-81.
3. Sudoh T, Minamino N, Kangawa W, et al. C-type natriuretic peptide (CNP):A new member of natriuretic peptide family identified in porcine brain[J]. Bichem Biophys Res Commun,1990,168:863-870.
4. Schweitz H, Vigne P, Moinier D. A new member of the natriuretic peptide family is present in the venom of the green mamba (Dendroaspis angusticeps) [J]. J Biol Chem, 1992,267:13928-13932.
5. Wei CM, Kim CH, Miller VM, et al. Vasonatrin peptide:a unique synthetic natriuretic and vasorelaxing peptide. J Clin Invest.1993,92(4):2048-2052.
6. Sudoh T, Minamino N, Kangawa K, et al. C-type natriuretic peptide (CNP):a new member of natriuretic peptide family identified in porcine brain. Biochem Biophys Res Commun.1990,168(2):863-870.
7. Terada Y, Tomita K, Nonoguchi H, et al. PCR localization of C-type natriuretic peptide and B-type receptor mRNAs in rat nephron segments. Am J Physiol.1994,267(2 Pt 2): F215-222.
8. Suzuki E, Hirata Y, Hayakawa H, et al. Evidence for C-type natriuretic peptide production in the rat kidney. Biochem Biophys Res Commun.1993,192(2):532-538
9. Kar NL,Josephe KL,Timothy GY. Gene expression and synthesis of natriuretic peptide by cultured human glomular hyperters.1999,17:575-583
10. Lohe A, Yeh I, Hyver T, et al. Natriuretic peptide B receptor and C-type natriuretic peptide in the rat kidney. J Am SocNephrol.1995,6(6):1552-1558.
11. Cahill PA, Hassid A. Clearance receptor-binding atrial natriuretic peptides inhibit mitogenesis and proliferation of rat aortic smooth muscle cells. Biochem Biophys Res Commun.1991,179(3):1606-1613.
12. Levin ER. Natriuretic peptide C-receptor:more than a clearance receptor. Am J Physiol. 1993,264(4 Pt 1):E483-489.
13. Levin ER, Gardner DG, Samson WK. Natriuretic peptides. N Engl J Med.1998,339(5): 321-328.
14. Chen HH, Burnett JC Jr. C-type natriuretic peptide:the endothelial component of the natriuretic peptide system. J Cardiovasc Pharmacol.1998,3:S22-28.
15.姚建,曹红娣,王伟.人肾小球系膜细胞利钠肽受体表达的研究.上海第二医科大学学报,1998,17：479-480.
16. Lewko B, Endlich N, Kriz W, et al. C-type natriuretic peptide as a podocyte hormone and modulation of its cGMP production by glucose and mechanical stress. Kidney Int. 2004,66(3):1001-1008.
17. Sansoe G, Aragno M, Mastrocola R, et al. Overexpression of kidney neutral endopeptidase (EC 3.4.24.11) and renal function in experimental cirrhosis. Am J Physiol Renal Physiol.2006,290(6):F1337-1343.
18. Roubert P, Lonchampt MO, Chabrier PE, et al. Down-regulation of atrial natriuretic factor receptors and correlation with cGMP stimulation in rat cultured vascular smooth muscle cells. Biochem Biophys Res Commun.1987,148(1):61-67.
19. Hagiwara H, Inoue A, Furuya M, et al. Change in the expression of C-type natriuretic peptide and its receptor, B-type natriuretic peptide receptor, during dedifferentiation of chondrocytes into fibroblast-like cells. J Biochem.1996,119(2):264-267.
20. Yoshimoto T, Naruse M, Naruse K, et al. Modulation of vascular natriuretic peptide receptor gene expression in hypertensive and obese hyperglycemic rats. Endocrinology. 1995,136(6):2427-2434.
21. Nuglozeh E, Mbikay M, Stewart DJ, et al. Rat natriuretic peptide receptor genes are regulated by glucocorticoids in vitro. Life Sci.1997,61(22):2143-2155.
22. Mistry SK, Chatterjee PK, Weerackody RP, et al. Evidence for atrial natriuretic factor induced natriuretic peptide receptor subtype switching in rat proximal tubular cells during culture. Exp Nephrol.1998,6(2):104-111.
23. Kato J, Lanier-Smith KL, Currie MG. Cyclic GMP down-regulates atrial natriuretic peptide receptors on cultured vascular endothelial cells. J Biol Chem.1991,266(22): 14681-14685.
24. Zhang LM, Tao H, Newman WH. Regulation of atrial natriuretic peptide receptors in vascular smooth muscle cells:role of cGMP. Am J Physiol.1993,264(6 Pt 2): H1753-1759.
25. Yasunari K, Kohno M, Murakawa K, et al. Phorbol ester and atrial natriuretic peptide receptor response on vascular smooth muscle. Hypertension.1992,19(4):314-319.
26. Fujio N, Gossard F, Bayard F, et al. Regulation of natriuretic peptide receptor A and B expression by transforming growth factor-beta 1 in cultured aortic smooth muscle cells. Hypertension.1994,23(6 Pt 2):908-913.
27. Cao L, Zlock DW, Gardner DG. Differential regulation of natriuretic peptide receptor activity in vascular cells. Hypertension.1994,24(3):329-338
28. Cao L, Wu J, Gardner DG. Atrial natriuretic peptide suppresses the transcription of its guanylyl cyclase-linked receptor. J Biol Chem.1995,270(42):24891-24897
29. Brown LA, Nunez DJ, Wilkins MR. Differential regulation of natriuretic peptide receptor messenger RNAs during the development of cardiac hypertrophy in the rat. J Clin Invest.1993,92(6):2702-2712.
30. Suga S, Nakao K, Kishimoto I, et al. Phenotype-related alteration in expression of natriuretic peptide receptors in aortic smooth muscle cells. Circ Res.1992,71(1): 34-39.
31. Yoshimoto T, Naruse M, Naruse K, et al. Angiotensin Ⅱ-dependent down-regulation of vascular natriuretic peptide type C receptor gene expression in hypertensive rats. Endocrinology.1996,137(3):1102-1107.
32. Supaporn T, Wennberg PW, Wei CM, et al. Role for the endogenous natriuretic peptide system in the control of basal coronary vascular tone in dogs. Clin Sci (Lond).1996, 90(5):357-362.
33. Yokota N, Bruneau BG, Kuroski de Bold ML, et al. Atrial natriuretic factor significantly contributes to the mineralocorticoid escape phenomenon. Evidence for a guanylate cyclase-mediated pathway. J Clin Invest.1994,94(5):1938-1946.
34. Lopez MJ, Wong SK, Kishimoto I, et al. Salt-resistant hypertension in mice lacking the guanylyl cyclase-A receptor for atrial natriuretic peptide. Nature.1995,378(6552): 65-68.
35. John SW, Krege JH, Oliver PM, et al. Genetic decreases in atrial natriuretic peptide and salt-sensitive hypertension. Science.1995,267(5198):679-681.
36. Steinhelper ME, Cochrane KL, Field LJ. Hypotension in transgenic mice expressing atrial natriuretic factor fusion genes. Hypertension.1990,16(3):301-307.
37. Field LJ, Veress AT, Steinhelper ME, et al. Kidney function in ANF-transgenic mice: effect of blood volume expansion. Am J Physiol.1991,260(1 Pt 2):R1-5.
38.40 Phain I, Sediame S, Maistre G, et al. Renal and vascular effects Of C-type and atrial natriuretic peptides in humans [J]. Am J Physiol,1997,273(4 Pt 2):R1457-1464.
39. Akashi YJ, Springer J, Lainscak M, et al. Atrial natriuretic peptide and related peptides. Clin Chem Lab Med.2007,45(10):1259-1267.
40. Lee SJ, Kim SZ, Cui X, et al. C-type natriuretic peptide inhibits ANP secretion and atrial dynamics in perfused atria:NPR-B-cGMP signaling. Am J Physiol Heart Circ Physiol.2000,278(1):H208-221.
41. Cataliotti A, Giordano M, De Pascale E, et al. CNP production in the kidney and effects of protein intake restriction in nephrotic syndrome. Am J Physiol Renal Physiol. 2002,283(3):F464-472.
42.裴晓阳综述冯建章审校.钠尿肽家族及其生理功能.血管病杂志2004,10(1)：67-69.
43. Giilberg V, Moller S, Henriksen JH, et al. Increased renal production of C-type natriuretic peptide (CNP) in patients with cirrhosis and functional renal failure. Gut. 2000,47(6):852-857.
44. Wei CM, Hu S, Miller VM, et al. Vascular actions of C-type natriuretic peptide in isolated porcine coronary arteries and coronary vascular smooth muscle cells. Biochem Biophys Res Commun.1994,205(1):765-771.
45. Wei CM, Aarhus LL, Miller VM, et al. Action of C-type natriuretic peptide in isolated canine arteries and veins. Am J Physiol.1993,264(1 Pt 2):H71-73.
46. Del Ry S, Maltinti M, Cabiati M, et al. C-type natriuretic peptide and its relation to non-invasive indices of left ventricular function in patients with chronic heart failure. Peptides.2008,29(1):79-82.
47. Del Ry S, Maltinti M, Piacenti M, et al. Cardiac production of C-type natriuretic peptide in heart failure. J Cardiovasc Med (Hagerstown).2006,7(6):397-399.
48. Passino C, Del Ry S, Severino S, et al. C-type natriuretic peptide expression in patients with chronic heart failure:effects of aerobic training. Eur J Cardiovasc Prev Rehabil. 2008,15(2):168-172.
49.袁鼎山,景宏美,李爱林,等.心力衰竭患者c型利钠肽水平与心功能的关系[J].郑苏州大学学报(医学版),2007,27(3)：420-421.
50.王敬民,徐青,钟磊.血浆C型利钠肽在充血性心力衰竭中的临床价值[J].浙江临床医学,2003,5(12)：892-194.
51.段桂琴,从娟,安金斗.慢性心力衰竭患儿血浆肾上腺髓质素、C型利钠肽及心肌作功指数测定[J].郑州大学学报(医学版),2007,42(4)：694-696.
52. Trachte GJ, Drewett JG. C-type natriuretic peptide neuromodulates independently of guanylyl cyclase activation. Hypertension.1994,23(1):38-43.
53. Nir A, Beers KW, Clavell AL, et al. CNP is present in canine renal tubular cells and secreted by cultured opossum kidney cells. Am J Physiol.1994,267(6 Pt 2): R1653-1657.
54. Clavell AL, Stingo AJ, Wei CM, et al. C-type natriuretic peptide:a selective cardiovascular peptide. Am J Physiol.1993,264(2 Pt 2):R290-295.
55. Charles CJ, Richards AM, Espiner EA. Central C-type natriuretic peptide but not atrial natriuretic factor lowers blood pressure and adrenocortical secretion in normal conscious sheep, Endocrinology.1992,131(4):1721-1726.
56.李付远,季乃军,梅益斌,等.原发性高血压患者血清C型利钠肽变化及其临床意义[J].放射免疫学杂志,2005,14(3)：222-225.
57.景宏美,袁鼎山,贾春文,等.C型利钠肽在高血压病患者中的变化及其临床意义[J].中华老年多器官疾病杂志,2006,(4)：273-275.
58.赵杰娉,崔天祥,李莉.C型利钠肽与原发性高血压左室舒张功能障碍的关系[J].中国实用神经疾病杂杂,2006,9(7)：57-58.
59.杨丛芝,包晓群,由春梅,等.原发性高血压患者C型利钠肽与左室舒张功能的关 系[J].中国老年学杂志,2008,28(11)：1129-1130.
60.宋成伟.原发性高血压患者C型利钠肽与左室舒张功能的关系[J].中国实验诊断学,2007,11(9)：1197-1198.
61.王晓红,陈亚红,齐永芬,等.血管活性物质对人内皮细胞c型利钠利尿肽合成和释放的影响[J].中国病理生理杂志,2001,17(3)：193-195.
62.赵海鹰,王浩,范珂,等.原发性高血压与血浆c型利钠肽的表达[J].河南医学研究,2002,11(2)：132-134.
63. Burnett JC Jr. Vasopeptidase inhibition:a new concept in blood pressure management. J Hypertens Suppl.1999,17(1):S37-43.
64. Jones CA, McQuillan GM, et al. Serum creatinine levels in the US population:third National Health and Nutrition Examination Survey. Am J Kidney Dis. 1998,32(6):992-999.
65. Vickery S, Price CP, John RI, et al. B-type natriuretic peptide (BNP) and amino-terminal proBNP in patients with CKD:relationship to renal function and left ventricular hypertrophy. Am J Kidney Dis.2005,46(4):610-620.
66. Zeng C, Wei T, Jin L, et al. Value of B-type natriuretic peptide in diagnosing left ventricular dysfunction in dialysis-dependent patients. Intern Med J.2006,36(9): 552-557.
67. Cataliotti A, Malatino LS, Jougasaki M, et al. Circulating natriuretic peptide concentrations in patients with end-stage renal disease:role of brain natriuretic peptide as a biomarker for ventricular remodeling. Mayo ClinProc.2001,76(11):1111-1119.
68. Wang AY, Lam CW, Yu CM, et al.. N-terminal pro-brain natriuretic peptide:an independent risk predictor of cardiovascular congestion, mortality, and adverse cardiovascular outcomes in chronic peritoneal dialysis patients. J Am Soc Nephrol. 2007,18(1):321-330.
69.周文彦,倪兆慧,方炜.慢性肾脏病非透析患者脑钠素与动脉粥样硬化及心功能的关系[J].中华肾脏病杂志,2007,23(4)：162.
70. Naganuma T, Sugimura K, Wada S, et al. The prognostic role of brain natriuretic peptides in hemodialysis patients. Am J Nephrol.2002,22(5-6):437-444.
71. Takami Y, Horio T, Iwashima Y, et al. Diagnostic and prognostic value of plasma brain natriuretic peptide in non-dialysis-dependent CRF. Am J Kidney Dis.2004,44(3): 420-428.
72. Arjona AA, Hsu CA, Wrenn DS, et al. Effects of natriuretic peptides on vascular smooth-muscle cells derived from different vascular beds. Gen Pharmacol.1997,28(3): 387-392.
73. Calderone A, Thaik CM, Takahashi N, et al. Nitric oxide, atrial natriuretic peptide, and cyclic GMP inhibit the growth-promoting effects of norepinephrine in cardiac myocytes and fibroblasts. J Clin Invest.1998,101(4):812-818.
74. Cao L, Gardner DG. Natriuretic peptides inhibit DNA synthesis in cardiac fibroblasts. Hypertension.1995,25(2):227-234.
75. Neuser D, Stasch JP, Knorr A, et al. Inhibition by atrial natriuretic peptide of endothelin-1-stimulated proliferation of vascular smooth-muscle cells. J Cardiovasc Pharmacol.1993,8:S257-261.
76. Porter JQ Catalano R, McEnroe G, et al.. C-type natriuretic peptide inhibits growth factor-dependent DNA synthesis in smooth muscle cells. Am J Physiol.1992,263(5 Pt 1):C1001-1006.
77. Fujisaki H, Ito H, Hirata Y, et al. Natriuretic peptides inhibit angiotensin Ⅱ-induced proliferation of rat cardiac fibroblasts by blocking endothelin-1 gene expression. J Clin Invest.1995,96(2):1059-1065.
78. Kohno M, Yokokawa K, Yasunari K, et al. Effect of natriuretic peptide family on the oxidized LDL-induced migration of human coronary artery smooth muscle cells. Circ Res.1997,81(4):585-590.
79.吴建明,孙双丹,成彤,等.心钠素对内皮素促大鼠心肌细胞增殖的影响.中国应用生理学杂志,1992,(1)：87-88.
80. Iimura O, Kusano E, Homma S, et al. Atrial natriuretic peptide enhances IL-1 beta-stimulated nitric oxide production in cultured rat vascular smooth muscle cells. Kidney Blood Press Res.1998,21(1):36-41.
81. Hutchinson HG, Trindade PT, Cunanan DB, et al. Mechanisms of natriuretic-peptide-induced growth inhibition of vascular smooth muscle cells. Cardiovasc Res.1997,35(1):158-167.
82. Kumar R, Cartledge WA, Lincoln TM, et al. Expression of guanylyl cyclase-A/atrial natriuretic peptide receptor blocks the activation of protein kinase C in vascular smooth muscle cells. Role of cGMP and cGMP-dependent protein kinase. Hypertension.1997,29(1 Pt2):414-421.
83. Demoliou-Mason CD. G-protein-coupled receptors in vascular smooth muscle cells. Biol Signals Recept.1998,7(2):90-97.
84. Pandey KN. Atrial natriuretic factor inhibits autophosphorylation of protein kinase C and A 240-kDa protein in plasma membranes of bovine adrenal glomerulosa cells: involvement of cGMP-dependent and independent signal transduction mechanisms. Mol Cell Biochem.1994,141(2):103-111
85. Sano T, Imura R, Morishita Y, et al. HS-142-1, a novel polysaccharide of microbial origin, specifically recognizes guanylyl cyclase-linked ANP receptor in rat glomeruli. LifeSci.1992,51(18):1445-1451.
86. Ohyama Y, Miyamoto K, Morishita Y, et al. Stable expression of natriuretic peptide receptors:effects of HS-142-1, a non-peptide ANP antagonist. Biochem Biophys Res Commun.1992,189(1):336-342.
87. Morishita Y, Sano T, Ando K, Microbial polysaccharide, HS-142-1, competitively and selectively inhibits ANP binding to its guanylyl cyclase-containing receptor. Biochem Biophys Res Commun.1991,176(3):949-957.
88. Doi K, Ikeda T, Itoh H, et al. C-type natriuretic peptide induces redifferentiation of vascular smooth muscle cells with accelerated reendothelialization.Arterioscler Thromb Vasc Biol.2001,21(6):930-936.
89. Chujo K, Ueno M, Asaga T, et al. Atrial natriuretic peptide enhances recovery from ischemia/reperfusion-induced renal injury in rats. J Biosci Bioeng.2010,109(6): 526-530.
90. Chujo K, Ueki M, Asaga T, et al. Atrial natriuretic peptide attenuates ischemia/reperfusion-induced renal injury by reducing neutrophil activation in rats. Tohoku J Exp Med.2008,215(3):257-266.
91. Takei Y, Takahashi A, Watanabe TX, et al. A novel natriuretic peptide isolated from eel cardiac ventricles. FEBS Lett.1991,282(2):317-320.
92. Takei Y. [Structure and function of ventricular natriuretic peptide (VNP)]. Nippon Rinsho.1992,50(3):656-663.
93. Takei Y, Ueki M, Nishizawa T. Eel ventricular natriuretic peptide:cDNA cloning and mRNA expression. J Mol Endocrinol.1994,13(3):339-345.
94. Arai M, Goto F, Takei Y. Effect of eel ventricular natriuretic peptide on the kidney and cardiovascular system in the dog. Endocr J.1996,43(2):205-210.
95. Schweitz H,Vigene P, Moinier D,et al. A new member of the natriuretic peptide family is present in the venom of the green mamba (Dendroaspis angusticeps). J Biol Chem 1992,267(20):13928-13932.
96. Takei Y, Takano M, Itahara Y, et al. Rainbow trout ventricular natriuretic peptide: isolation, sequencing, and determination of biological activity. Gen Comp Endocrinol. 1994,96(3):420-426.
97. Schirger JA, Heublein DM, Chen HH, et al. Presence of Dendroaspis natriuretic peptide-like immunoreactivity in human plasma and its increase during human heart failure. Mayo Clin Proc.1999,74(2):126-130.
98. Lisy O, Jougasaki M, Heublein DM, et al. Renal actions of synthetic dendroaspis natriuretic peptide. Kidney Int.1999,56(2):502-508.
99. Wei CM, Kim CH, Miller VM, Burnett JC Jr. Vasonatrin peptide:a unique synthetic natriuretic and vasorelaxing peptide. J Clin Invest.1993,92(4):2048-2052.
100.冯华松,臧益民,朱妙章,等.血管利钠肽对大鼠肺动脉的舒张作用及机制.心功能杂志,1998,10(2)：67-71.
101.冯华松,臧益民,朱妙章.血管钠肽、C型钠尿肽和心房钠尿肽舒血管作用的对比.生理学报,1999,51(5)：515-520.
102.冯华松,臧益民,朱妙章,等.血管利钠肽对慢性低氧大鼠离体血管条的舒张作用.第四军医大学学报,1998,19(4)：398-401.
2. Ramesh G, Reeves WB. Inflammatory cytokines in acute renal failure. Kidney Int Suppl.2004,(91):S56-61.
3. Furuichi K, Wada T, Yokoyama H, et al. Role of Cytokines and Chemokines in Renal Ischemia-Reperfusion Injury. Drug News Perspect.2002,15(8):477-482.
4. Liangos O, Tighiouart H, Perianayagam MC, et al. Comparative analysis of urinary biomarkers for early detection of acute kidney injury following cardiopulmonary bypass. Biomarkers.2009,14(6):423-431.
5. Burne-Taney MJ, Rabb H. The role of adhesion molecules and T cells in ischemic renal injury. Curr OpinNephrol Hypertens.2003,12(1):85-90.
6. Ysebaert DK, De Greef KE, De Beuf A, et al. T cells as mediators in renal ischemia/reperfusion injury. Kidney Int.2004,66(2):491-496.
7. Friedewald JJ, Rabb H. Inflammatory cells in ischemic acute renal failure. Kidney Int. 2004,66(2):486-491.
8. Bonventre JV, Zuk A. Ischemic acute renal failure:an inflammatory disease? Kidney Int.2004,66(2):480-485.
9. Singbartl K, Ley K. Leukocyte recruitment and acute renal failure. J Mol Med.2004, 82(2):91-101.
10. Andreucci M, Michael A, Kramers C, et al. Renal ischemia/reperfusion and ATP depletion/repletion in LLC-PK(1) cells result in phosphorylation of FKHR and FKHRL1. Kidney Int.2003,64(4):1189-1198.
11. Tilney NL, Guttmann RD. Effects of initial ischemia/reperfusion injury on the transplanted kidney. Transplantation.1997,64(7):945-947.
12. Okusa MD. The inflammatory cascade in acute ischemic renal failure. Nephron.2002, 90(2):133-138.
13. Arumugam TV, Shiels IA, Woodruff TM, et al. The role of the complement system in ischemia-reperfusion injury. Shock.2004,21(5):401-409.
14. Yamada K, Miwa T, Liu J, et al. Critical protection from renal ischemia reperfusion injury by CD55 and CD59. J Immunol.2004,172(6):3869-3875.
15. Thurman JM, Ljubanovic D, Edelstein CL, et al. Lack of a functional alternative complement pathway ameliorates ischemic acute renal failure in mice. J Immunol. 2003,170(3):1517-1523.
16. Arumugam TV, Shiels IA, Strachan AJ, et al. A small molecule C5a receptor antagonist protects kidneys from ischemia/reperfusion injury in rats. Kidney Int.2003,63(1): 134-142.
17. di Mari JF, Davis R, Safirstein RL. MAPK activation determines renal epithelial cell survival during oxidative injury. Am J Physiol.1999,277(2 Pt 2):F195-203.
18. De Bold, AJ, Borenstein HB, Veress AT, et al. A rapid and potent natriuretic response to intravenous injection of atrial myocardial extracts in rats. Life Sci.1981,28:89-94.
19. Sudoh T, Kangawa K, Minamino N, et al. A new natriuretic peptide in porcine brain[J]. Nature.1988,322(6159):78-81.
20. Sudoh T, Minamino N, Kangawa W, et al. C-type natriuretic peptide (CNP):A new member of natriuretic peptide family identified in porcine brain[J]. Bichem Biophys Res Commun.1990,168(2):863-870.
21. Schweitz H, Vigne P, Moinier D, et al. A new member of the natriuretic peptide family is present in the venom of the green mamba (Dendroaspis angusticeps) [J]. J Biol Chem.1992,267(20):13928-13932.
22. Cahill PA, Hassid A. Clearance receptor-binding atrial natriuretic peptides inhibit mitogenesis and proliferation of rat aortic smooth muscle cells. Biochem Biophys Res Commun.1991,179(3):1606-1613.
23. Levin ER. Natriuretic peptide C-receptor:more than a clearance receptor. Am J Physiol. 1993,264(4 Pt 1):E483-489.
24. Chujo K, Ueno M, Asaga T, et al. Atrial natriuretic peptide enhances recovery from ischemia/reperfusion-induced renal injury in rats. J Biosci Bioeng.2010,109(6): 526-530.
25. Chujo K, Ueki M, Asaga T, et al. Atrial natriuretic peptide attenuates ischemia/reperfusion-induced renal injury by reducing neutrophil activation in rats. Tohoku J Exp Med.2008,215(3):257-266.
26. Yoshimoto T, Naruse M, Naruse K, et al. Modulation of vascular natriuretic peptide receptor gene expression in hypertensive and obese hyperglycemic rats. Endocrinology.1995,136(6):2427-2434.
27. Kar NL,Josephe KL,Timothy GY. Gene expression and synthesis of natriuretic peptide by cultured human glomular hyperters.1999,17:575-583
28. Lohe A, Yeh I, Hyver T, et al. Natriuretic peptide B receptor and C-type natriuretic peptide in the rat kidney. J Am Soc Nephrol.1995,6(6):1552-1558.
29. Igaki T, Itoh H, Suga S, et al. C-type natriuretic peptide in chronic renal failure and its action in humans. Kidney Int 49.1996,55:S144-S147,
30. Lai FJ, Hsieh MC, Hsin SC,et al. The cellular localization of increased atrial natriuretic peptide mRNA and immunoreactivity in diabetic rat kidneys. J Histochem Cytochem. 2002,50(11):1501-1508.
31. Terada Y, Tomita K, Nonoguchi H, et al. PCR localization of C-type natriuretic peptide and B-type receptor mRNAs in rat nephron segments. Am J Physiol.1994,267(2 Pt 2): F215-222.
32. Suzuki E, Hirata Y, Hayakawa H, et al. Evidence for C-type natriuretic peptide production in the rat kidney. Biochem Biophys Res Commun.1993,192(2):532-538
33. Kar NL,Josephe KL,Timothy GY. Gene expression and synthesis of natriuretic peptide by cultured human glomular hyperters.1999,17:575-583
34. Giilberg V, M(?)ller S, Henriksen JH, et al. Increased renal production of C-type natriuretic peptide (CNP) in patients with cirrhosis and functional renal failure. Gut. 2000,47(6):852-857.
35. Sansoe G, Aragno M, Mastrocola R, et al. Overexpression of kidney neutral endopeptidase (EC 3.4.24.11) and renal function in experimental cirrhosis. Am J Physiol Renal Physiol.2006,290(6):F1337-1343.
36. Chen HH, Burnett JC Jr. C-type natriuretic peptide:the endothelial component of the natriuretic peptide system. J Cardiovasc Pharmacol.1998,3:S22-28.
37. Lohe A, Yeh I, Hyver T, et al. Natriuretic peptide B receptor and C-type natriuretic peptide in the rat kidney. J Am Soc Nephrol.1995,6(6):1552-1558.
38. Datta SR, Brunet A, Greenberg ME. Cellular survival:a play in three Akts. Genes Dev. 1999,13(22):2905-2927.
39. Cross TG, Scheel-Toellner D, Henriquez NV, et al. Serine/threonine protein kinases and apoptosis. Exp Cell Res.2000,256(1):34-41.
40. Andreucci M, Michael A, Kramers C, et al. Renal ischemia/reperfusion and ATP depletion/repletion in LLC-PK(1) cells result in phosphorylation of FKHR and FKHRL1. Kidney Int.2003,64(4):1189-1198.
1. Kucuk A, Kabadere S, Tosun M, et al. Protective effects of doxycycline in ischemia/reperfusion injury on kidney. J Physiol Biochem.2009,65(2):183-191.
2. Ramesh G, Reeves WB. Inflammatory cytokines in acute renal failure. Kidney Int Suppl.2004, (91):S56-61.
3. Furuichi K, Wada T, Yokoyama H, et al. Role of Cytokines and Chemokines in Renal Ischemia-Reperfusion Injury. Drug News Perspect.2002,15(8):477-482.
4. Liangos O, Tighiouart H, Perianayagam MC, et al. Comparative analysis of urinary biomarkers for early detection of acute kidney injury following cardiopulmonary bypass. Biomarkers.2009,14(6):423-431.
5. Chujo K, Ueno M, Asaga T, et al. Atrial natriuretic peptide enhances recovery from ischemia/reperfusion-induced renal injury in rats. J Biosci Bioeng.2010,109(6): 526-530.
6. Chujo K, Ueki M, Asaga T, et al. Atrial natriuretic peptide attenuates ischemia/reperfusion-induced renal injury by reducing neutrophil activation in rats. Tohoku J Exp Med.2008,215(3):257-266.
7. Sudoh T, Minamino N, Kangawa K, et al. C-type natriuretic peptide (CNP):a new member of natriuretic peptide family identified in porcine brain. Biochem Biophys Res Commun.1990,168(2):863-870.
8. Gulberg V, M(?)ller S, Henriksen JH, et al. Increased renal production of C-type natriuretic peptide (CNP) in patients with cirrhosis and functional renal failure. Gut. 2000,47(6):852-857.
9. Igaki T, Itoh H, Suga S, et al. C-type natriuretic peptide in chronic renal failure and its action in humans. Kidney Int 49.1996,55:S144-S147.
10. Holleyman CR, Larson DF. Apoptosis in the ischemic reperfused myocardium. Perfusion.2001,16(6):491-502.
11. Schramm L, Heidbreder E, Lukes M, et al. Endotoxin-induced acute renal failure in the rat:effects of urodilatin and diltiazem on renal function. Clin Nephrol.1996,46(2): 117-124.
12. Spek CA, Bruggemann LW, Borensztajn KS. Protease-activated receptor 2 blocking peptide counteracts endotoxin-induced inflammation and coagulation and ameliorates renal fibrin deposition in a rat model of acute renal failure. Shock.2010,33(3):339.
13. Hengartner MO. The biochemistry of apoptosis. Nature.2000,407(6805):770-776.
14. Thornberry NA, Lazebnik Y. Caspases:enemies within. Science.1998,281(5381): 1312-1316.
15. Kaushal GP, Kaushal V, Hong X,,et al. Role and regulation of activation of caspases in cisplatin-induced injury to renal tubular epithelial cells. Kidney Int.2001,60(5): 1726-1736.
16. Bonegio R, Lieberthal W. Role of apoptosis in the pathogenesis of acute renal failure. Curr Opin Nephrol Hypertens.2002,11(3):301-308.
17. Saikumar P, Venkatachalam MA. Role of apoptosis in hypoxic/ischemic damage in the kidney. Semin Nephrol.2003,23(6):511-521.
18. Eschwege P, Paradis V, Conti M, et al. Bcl-2 and Bax expression on rat ischemic kidney.Transplant Proc.1998,30(6):2861-2862.
19.史明,张文岚,薄立华.肾缺血再灌注细胞内钙水平与氧化应激损伤研究[J].中国生物制品学杂志,2003,16(5)：311-313.
20.傅耀文,张文岚,薛立娟等.缺血再灌注对肾细胞内钙水平与细胞凋亡的影响[J].中华泌尿外科杂志,2004,25(12)：834-837.
21. Chatterjee PK, Brown PA, Cuzzocrea S, et al. Calpain inhibitor-1 reduces renal ischemia/reperfusion injury in the rat. Kidney Int.2001,59(6):2073-2083.
22. Jiang S, Chen Y, Zou J, et al. Diverse effects of ischemic pretreatments on the long-term renal damage induced by ischemia-reperfusion. Am J Nephrol.2009,30(5): 440-449.
1. De Bold, AJ, Borenstein HB, et al. Sonnenberg H. A rapid and potent natriuretic response to intravenous injection of atrial myocardial extracts in rats[J]. Life Sci,1981, 28(1):89-94.
2. Sudoh T, Kangawa K, Minamino N, et al. A new natriuretic peptide in porcine brain[J]. Nature,1988,322(6159):78-81.
3. Sudoh T, Minamino N, Kangawa W, et al. C-type natriuretic peptide (CNP):A new member of natriuretic peptide family identified in porcine brain[J]. Bichem Biophys Res Commun,1990,168:863-870.
4. Schweitz H, Vigne P, Moinier D. A new member of the natriuretic peptide family is present in the venom of the green mamba (Dendroaspis angusticeps) [J]. J Biol Chem, 1992,267:13928-13932.
5. Wei CM, Kim CH, Miller VM, et al. Vasonatrin peptide:a unique synthetic natriuretic and vasorelaxing peptide. J Clin Invest.1993,92(4):2048-2052.
6. Sudoh T, Minamino N, Kangawa K, et al. C-type natriuretic peptide (CNP):a new member of natriuretic peptide family identified in porcine brain. Biochem Biophys Res Commun.1990,168(2):863-870.
7. Terada Y, Tomita K, Nonoguchi H, et al. PCR localization of C-type natriuretic peptide and B-type receptor mRNAs in rat nephron segments. Am J Physiol.1994,267(2 Pt 2): F215-222.
8. Suzuki E, Hirata Y, Hayakawa H, et al. Evidence for C-type natriuretic peptide production in the rat kidney. Biochem Biophys Res Commun.1993,192(2):532-538
9. Kar NL,Josephe KL,Timothy GY. Gene expression and synthesis of natriuretic peptide by cultured human glomular hyperters.1999,17:575-583
10. Lohe A, Yeh I, Hyver T, et al. Natriuretic peptide B receptor and C-type natriuretic peptide in the rat kidney. J Am SocNephrol.1995,6(6):1552-1558.
11. Cahill PA, Hassid A. Clearance receptor-binding atrial natriuretic peptides inhibit mitogenesis and proliferation of rat aortic smooth muscle cells. Biochem Biophys Res Commun.1991,179(3):1606-1613.
12. Levin ER. Natriuretic peptide C-receptor:more than a clearance receptor. Am J Physiol. 1993,264(4 Pt 1):E483-489.
13. Levin ER, Gardner DG, Samson WK. Natriuretic peptides. N Engl J Med.1998,339(5): 321-328.
14. Chen HH, Burnett JC Jr. C-type natriuretic peptide:the endothelial component of the natriuretic peptide system. J Cardiovasc Pharmacol.1998,3:S22-28.
15.姚建,曹红娣,王伟.人肾小球系膜细胞利钠肽受体表达的研究.上海第二医科大学学报,1998,17：479-480.
16. Lewko B, Endlich N, Kriz W, et al. C-type natriuretic peptide as a podocyte hormone and modulation of its cGMP production by glucose and mechanical stress. Kidney Int. 2004,66(3):1001-1008.
17. Sansoe G, Aragno M, Mastrocola R, et al. Overexpression of kidney neutral endopeptidase (EC 3.4.24.11) and renal function in experimental cirrhosis. Am J Physiol Renal Physiol.2006,290(6):F1337-1343.
18. Roubert P, Lonchampt MO, Chabrier PE, et al. Down-regulation of atrial natriuretic factor receptors and correlation with cGMP stimulation in rat cultured vascular smooth muscle cells. Biochem Biophys Res Commun.1987,148(1):61-67.
19. Hagiwara H, Inoue A, Furuya M, et al. Change in the expression of C-type natriuretic peptide and its receptor, B-type natriuretic peptide receptor, during dedifferentiation of chondrocytes into fibroblast-like cells. J Biochem.1996,119(2):264-267.
20. Yoshimoto T, Naruse M, Naruse K, et al. Modulation of vascular natriuretic peptide receptor gene expression in hypertensive and obese hyperglycemic rats. Endocrinology. 1995,136(6):2427-2434.
21. Nuglozeh E, Mbikay M, Stewart DJ, et al. Rat natriuretic peptide receptor genes are regulated by glucocorticoids in vitro. Life Sci.1997,61(22):2143-2155.
22. Mistry SK, Chatterjee PK, Weerackody RP, et al. Evidence for atrial natriuretic factor induced natriuretic peptide receptor subtype switching in rat proximal tubular cells during culture. Exp Nephrol.1998,6(2):104-111.
23. Kato J, Lanier-Smith KL, Currie MG. Cyclic GMP down-regulates atrial natriuretic peptide receptors on cultured vascular endothelial cells. J Biol Chem.1991,266(22): 14681-14685.
24. Zhang LM, Tao H, Newman WH. Regulation of atrial natriuretic peptide receptors in vascular smooth muscle cells:role of cGMP. Am J Physiol.1993,264(6 Pt 2): H1753-1759.
25. Yasunari K, Kohno M, Murakawa K, et al. Phorbol ester and atrial natriuretic peptide receptor response on vascular smooth muscle. Hypertension.1992,19(4):314-319.
26. Fujio N, Gossard F, Bayard F, et al. Regulation of natriuretic peptide receptor A and B expression by transforming growth factor-beta 1 in cultured aortic smooth muscle cells. Hypertension.1994,23(6 Pt 2):908-913.
27. Cao L, Zlock DW, Gardner DG. Differential regulation of natriuretic peptide receptor activity in vascular cells. Hypertension.1994,24(3):329-338
28. Cao L, Wu J, Gardner DG. Atrial natriuretic peptide suppresses the transcription of its guanylyl cyclase-linked receptor. J Biol Chem.1995,270(42):24891-24897
29. Brown LA, Nunez DJ, Wilkins MR. Differential regulation of natriuretic peptide receptor messenger RNAs during the development of cardiac hypertrophy in the rat. J Clin Invest.1993,92(6):2702-2712.
30. Suga S, Nakao K, Kishimoto I, et al. Phenotype-related alteration in expression of natriuretic peptide receptors in aortic smooth muscle cells. Circ Res.1992,71(1): 34-39.
31. Yoshimoto T, Naruse M, Naruse K, et al. Angiotensin Ⅱ-dependent down-regulation of vascular natriuretic peptide type C receptor gene expression in hypertensive rats. Endocrinology.1996,137(3):1102-1107.
32. Supaporn T, Wennberg PW, Wei CM, et al. Role for the endogenous natriuretic peptide system in the control of basal coronary vascular tone in dogs. Clin Sci (Lond).1996, 90(5):357-362.
33. Yokota N, Bruneau BG, Kuroski de Bold ML, et al. Atrial natriuretic factor significantly contributes to the mineralocorticoid escape phenomenon. Evidence for a guanylate cyclase-mediated pathway. J Clin Invest.1994,94(5):1938-1946.
34. Lopez MJ, Wong SK, Kishimoto I, et al. Salt-resistant hypertension in mice lacking the guanylyl cyclase-A receptor for atrial natriuretic peptide. Nature.1995,378(6552): 65-68.
35. John SW, Krege JH, Oliver PM, et al. Genetic decreases in atrial natriuretic peptide and salt-sensitive hypertension. Science.1995,267(5198):679-681.
36. Steinhelper ME, Cochrane KL, Field LJ. Hypotension in transgenic mice expressing atrial natriuretic factor fusion genes. Hypertension.1990,16(3):301-307.
37. Field LJ, Veress AT, Steinhelper ME, et al. Kidney function in ANF-transgenic mice: effect of blood volume expansion. Am J Physiol.1991,260(1 Pt 2):R1-5.
38.40 Phain I, Sediame S, Maistre G, et al. Renal and vascular effects Of C-type and atrial natriuretic peptides in humans [J]. Am J Physiol,1997,273(4 Pt 2):R1457-1464.
39. Akashi YJ, Springer J, Lainscak M, et al. Atrial natriuretic peptide and related peptides. Clin Chem Lab Med.2007,45(10):1259-1267.
40. Lee SJ, Kim SZ, Cui X, et al. C-type natriuretic peptide inhibits ANP secretion and atrial dynamics in perfused atria:NPR-B-cGMP signaling. Am J Physiol Heart Circ Physiol.2000,278(1):H208-221.
41. Cataliotti A, Giordano M, De Pascale E, et al. CNP production in the kidney and effects of protein intake restriction in nephrotic syndrome. Am J Physiol Renal Physiol. 2002,283(3):F464-472.
42.裴晓阳综述冯建章审校.钠尿肽家族及其生理功能.血管病杂志2004,10(1)：67-69.
43. Giilberg V, Moller S, Henriksen JH, et al. Increased renal production of C-type natriuretic peptide (CNP) in patients with cirrhosis and functional renal failure. Gut. 2000,47(6):852-857.
44. Wei CM, Hu S, Miller VM, et al. Vascular actions of C-type natriuretic peptide in isolated porcine coronary arteries and coronary vascular smooth muscle cells. Biochem Biophys Res Commun.1994,205(1):765-771.
45. Wei CM, Aarhus LL, Miller VM, et al. Action of C-type natriuretic peptide in isolated canine arteries and veins. Am J Physiol.1993,264(1 Pt 2):H71-73.
46. Del Ry S, Maltinti M, Cabiati M, et al. C-type natriuretic peptide and its relation to non-invasive indices of left ventricular function in patients with chronic heart failure. Peptides.2008,29(1):79-82.
47. Del Ry S, Maltinti M, Piacenti M, et al. Cardiac production of C-type natriuretic peptide in heart failure. J Cardiovasc Med (Hagerstown).2006,7(6):397-399.
48. Passino C, Del Ry S, Severino S, et al. C-type natriuretic peptide expression in patients with chronic heart failure:effects of aerobic training. Eur J Cardiovasc Prev Rehabil. 2008,15(2):168-172.
49.袁鼎山,景宏美,李爱林,等.心力衰竭患者c型利钠肽水平与心功能的关系[J].郑苏州大学学报(医学版),2007,27(3)：420-421.
50.王敬民,徐青,钟磊.血浆C型利钠肽在充血性心力衰竭中的临床价值[J].浙江临床医学,2003,5(12)：892-194.
51.段桂琴,从娟,安金斗.慢性心力衰竭患儿血浆肾上腺髓质素、C型利钠肽及心肌作功指数测定[J].郑州大学学报(医学版),2007,42(4)：694-696.
52. Trachte GJ, Drewett JG. C-type natriuretic peptide neuromodulates independently of guanylyl cyclase activation. Hypertension.1994,23(1):38-43.
53. Nir A, Beers KW, Clavell AL, et al. CNP is present in canine renal tubular cells and secreted by cultured opossum kidney cells. Am J Physiol.1994,267(6 Pt 2): R1653-1657.
54. Clavell AL, Stingo AJ, Wei CM, et al. C-type natriuretic peptide:a selective cardiovascular peptide. Am J Physiol.1993,264(2 Pt 2):R290-295.
55. Charles CJ, Richards AM, Espiner EA. Central C-type natriuretic peptide but not atrial natriuretic factor lowers blood pressure and adrenocortical secretion in normal conscious sheep, Endocrinology.1992,131(4):1721-1726.
56.李付远,季乃军,梅益斌,等.原发性高血压患者血清C型利钠肽变化及其临床意义[J].放射免疫学杂志,2005,14(3)：222-225.
57.景宏美,袁鼎山,贾春文,等.C型利钠肽在高血压病患者中的变化及其临床意义[J].中华老年多器官疾病杂志,2006,(4)：273-275.
58.赵杰娉,崔天祥,李莉.C型利钠肽与原发性高血压左室舒张功能障碍的关系[J].中国实用神经疾病杂杂,2006,9(7)：57-58.
59.杨丛芝,包晓群,由春梅,等.原发性高血压患者C型利钠肽与左室舒张功能的关 系[J].中国老年学杂志,2008,28(11)：1129-1130.
60.宋成伟.原发性高血压患者C型利钠肽与左室舒张功能的关系[J].中国实验诊断学,2007,11(9)：1197-1198.
61.王晓红,陈亚红,齐永芬,等.血管活性物质对人内皮细胞c型利钠利尿肽合成和释放的影响[J].中国病理生理杂志,2001,17(3)：193-195.
62.赵海鹰,王浩,范珂,等.原发性高血压与血浆c型利钠肽的表达[J].河南医学研究,2002,11(2)：132-134.
63. Burnett JC Jr. Vasopeptidase inhibition:a new concept in blood pressure management. J Hypertens Suppl.1999,17(1):S37-43.
64. Jones CA, McQuillan GM, et al. Serum creatinine levels in the US population:third National Health and Nutrition Examination Survey. Am J Kidney Dis. 1998,32(6):992-999.
65. Vickery S, Price CP, John RI, et al. B-type natriuretic peptide (BNP) and amino-terminal proBNP in patients with CKD:relationship to renal function and left ventricular hypertrophy. Am J Kidney Dis.2005,46(4):610-620.
66. Zeng C, Wei T, Jin L, et al. Value of B-type natriuretic peptide in diagnosing left ventricular dysfunction in dialysis-dependent patients. Intern Med J.2006,36(9): 552-557.
67. Cataliotti A, Malatino LS, Jougasaki M, et al. Circulating natriuretic peptide concentrations in patients with end-stage renal disease:role of brain natriuretic peptide as a biomarker for ventricular remodeling. Mayo ClinProc.2001,76(11):1111-1119.
68. Wang AY, Lam CW, Yu CM, et al.. N-terminal pro-brain natriuretic peptide:an independent risk predictor of cardiovascular congestion, mortality, and adverse cardiovascular outcomes in chronic peritoneal dialysis patients. J Am Soc Nephrol. 2007,18(1):321-330.
69.周文彦,倪兆慧,方炜.慢性肾脏病非透析患者脑钠素与动脉粥样硬化及心功能的关系[J].中华肾脏病杂志,2007,23(4)：162.
70. Naganuma T, Sugimura K, Wada S, et al. The prognostic role of brain natriuretic peptides in hemodialysis patients. Am J Nephrol.2002,22(5-6):437-444.
71. Takami Y, Horio T, Iwashima Y, et al. Diagnostic and prognostic value of plasma brain natriuretic peptide in non-dialysis-dependent CRF. Am J Kidney Dis.2004,44(3): 420-428.
72. Arjona AA, Hsu CA, Wrenn DS, et al. Effects of natriuretic peptides on vascular smooth-muscle cells derived from different vascular beds. Gen Pharmacol.1997,28(3): 387-392.
73. Calderone A, Thaik CM, Takahashi N, et al. Nitric oxide, atrial natriuretic peptide, and cyclic GMP inhibit the growth-promoting effects of norepinephrine in cardiac myocytes and fibroblasts. J Clin Invest.1998,101(4):812-818.
74. Cao L, Gardner DG. Natriuretic peptides inhibit DNA synthesis in cardiac fibroblasts. Hypertension.1995,25(2):227-234.
75. Neuser D, Stasch JP, Knorr A, et al. Inhibition by atrial natriuretic peptide of endothelin-1-stimulated proliferation of vascular smooth-muscle cells. J Cardiovasc Pharmacol.1993,8:S257-261.
76. Porter JQ Catalano R, McEnroe G, et al.. C-type natriuretic peptide inhibits growth factor-dependent DNA synthesis in smooth muscle cells. Am J Physiol.1992,263(5 Pt 1):C1001-1006.
77. Fujisaki H, Ito H, Hirata Y, et al. Natriuretic peptides inhibit angiotensin Ⅱ-induced proliferation of rat cardiac fibroblasts by blocking endothelin-1 gene expression. J Clin Invest.1995,96(2):1059-1065.
78. Kohno M, Yokokawa K, Yasunari K, et al. Effect of natriuretic peptide family on the oxidized LDL-induced migration of human coronary artery smooth muscle cells. Circ Res.1997,81(4):585-590.
79.吴建明,孙双丹,成彤,等.心钠素对内皮素促大鼠心肌细胞增殖的影响.中国应用生理学杂志,1992,(1)：87-88.
80. Iimura O, Kusano E, Homma S, et al. Atrial natriuretic peptide enhances IL-1 beta-stimulated nitric oxide production in cultured rat vascular smooth muscle cells. Kidney Blood Press Res.1998,21(1):36-41.
81. Hutchinson HG, Trindade PT, Cunanan DB, et al. Mechanisms of natriuretic-peptide-induced growth inhibition of vascular smooth muscle cells. Cardiovasc Res.1997,35(1):158-167.
82. Kumar R, Cartledge WA, Lincoln TM, et al. Expression of guanylyl cyclase-A/atrial natriuretic peptide receptor blocks the activation of protein kinase C in vascular smooth muscle cells. Role of cGMP and cGMP-dependent protein kinase. Hypertension.1997,29(1 Pt2):414-421.
83. Demoliou-Mason CD. G-protein-coupled receptors in vascular smooth muscle cells. Biol Signals Recept.1998,7(2):90-97.
84. Pandey KN. Atrial natriuretic factor inhibits autophosphorylation of protein kinase C and A 240-kDa protein in plasma membranes of bovine adrenal glomerulosa cells: involvement of cGMP-dependent and independent signal transduction mechanisms. Mol Cell Biochem.1994,141(2):103-111
85. Sano T, Imura R, Morishita Y, et al. HS-142-1, a novel polysaccharide of microbial origin, specifically recognizes guanylyl cyclase-linked ANP receptor in rat glomeruli. LifeSci.1992,51(18):1445-1451.
86. Ohyama Y, Miyamoto K, Morishita Y, et al. Stable expression of natriuretic peptide receptors:effects of HS-142-1, a non-peptide ANP antagonist. Biochem Biophys Res Commun.1992,189(1):336-342.
87. Morishita Y, Sano T, Ando K, Microbial polysaccharide, HS-142-1, competitively and selectively inhibits ANP binding to its guanylyl cyclase-containing receptor. Biochem Biophys Res Commun.1991,176(3):949-957.
88. Doi K, Ikeda T, Itoh H, et al. C-type natriuretic peptide induces redifferentiation of vascular smooth muscle cells with accelerated reendothelialization.Arterioscler Thromb Vasc Biol.2001,21(6):930-936.
89. Chujo K, Ueno M, Asaga T, et al. Atrial natriuretic peptide enhances recovery from ischemia/reperfusion-induced renal injury in rats. J Biosci Bioeng.2010,109(6): 526-530.
90. Chujo K, Ueki M, Asaga T, et al. Atrial natriuretic peptide attenuates ischemia/reperfusion-induced renal injury by reducing neutrophil activation in rats. Tohoku J Exp Med.2008,215(3):257-266.
91. Takei Y, Takahashi A, Watanabe TX, et al. A novel natriuretic peptide isolated from eel cardiac ventricles. FEBS Lett.1991,282(2):317-320.
92. Takei Y. [Structure and function of ventricular natriuretic peptide (VNP)]. Nippon Rinsho.1992,50(3):656-663.
93. Takei Y, Ueki M, Nishizawa T. Eel ventricular natriuretic peptide:cDNA cloning and mRNA expression. J Mol Endocrinol.1994,13(3):339-345.
94. Arai M, Goto F, Takei Y. Effect of eel ventricular natriuretic peptide on the kidney and cardiovascular system in the dog. Endocr J.1996,43(2):205-210.
95. Schweitz H,Vigene P, Moinier D,et al. A new member of the natriuretic peptide family is present in the venom of the green mamba (Dendroaspis angusticeps). J Biol Chem 1992,267(20):13928-13932.
96. Takei Y, Takano M, Itahara Y, et al. Rainbow trout ventricular natriuretic peptide: isolation, sequencing, and determination of biological activity. Gen Comp Endocrinol. 1994,96(3):420-426.
97. Schirger JA, Heublein DM, Chen HH, et al. Presence of Dendroaspis natriuretic peptide-like immunoreactivity in human plasma and its increase during human heart failure. Mayo Clin Proc.1999,74(2):126-130.
98. Lisy O, Jougasaki M, Heublein DM, et al. Renal actions of synthetic dendroaspis natriuretic peptide. Kidney Int.1999,56(2):502-508.
99. Wei CM, Kim CH, Miller VM, Burnett JC Jr. Vasonatrin peptide:a unique synthetic natriuretic and vasorelaxing peptide. J Clin Invest.1993,92(4):2048-2052.
100.冯华松,臧益民,朱妙章,等.血管利钠肽对大鼠肺动脉的舒张作用及机制.心功能杂志,1998,10(2)：67-71.
101.冯华松,臧益民,朱妙章.血管钠肽、C型钠尿肽和心房钠尿肽舒血管作用的对比.生理学报,1999,51(5)：515-520.
102.冯华松,臧益民,朱妙章,等.血管利钠肽对慢性低氧大鼠离体血管条的舒张作用.第四军医大学学报,1998,19(4)：398-401.