Angiotensin II infusion induces nephrin expression changes and podocyte apoptosis
Angiotensin II infusion induces nephrin expression changes and podocyte apoptosis
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DOI：
10.1159/000113538
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发表时间：
2008-01-01
影响因子：
4.2
通讯作者：
Singhal, Pravin C.
中科院分区：
文献类型：
--
作者：
Jia, Junya;Ding, Guohua;Singhal, Pravin C.
背景/目的：在体外研究中，血管紧张素（Ang）II已被证明可促进足细胞凋亡。本研究评价了血管紧张素II输注对大鼠足细胞nephrin表达和凋亡的影响，以及血管紧张素II诱导的蛋白尿和系膜扩张的分子机制。方法：Sprague-Dawley大鼠随机分为生理盐水组和Ang II组（400 ng.kg（-1）.min（-1）），每组各10只。在第7、14、21和28天测量收缩压和尿蛋白及白蛋白排泄率。在第14天和第28天处死动物，并评价血清肌酐、肾脏病理变化、足细胞凋亡、肾nephrin mRNA和蛋白表达。结果：Ang Ⅱ灌流大鼠出现高血压和蛋白尿。在第14天，血管紧张素II灌注大鼠显示狭窄的裂缝隔膜，足细胞nephrin mRNA和蛋白质表达的增加，并改变其分布沿着足突。在第28天，血管紧张素II输注大鼠表现出凋亡足细胞的存在和nephrin mRNA和蛋白表达下降。nephrin的表达与足细胞凋亡数呈负相关（r =-0.63，p < 0.05）。结论：nephrin表达的改变可能在Ang Ⅱ诱导足细胞凋亡的发病机制中起一定作用。版权所有（C）2008 S. Karger AG，巴塞尔。
Background/Aim: In in vitro studies, angiotensin (Ang) II has been demonstrated to promote podocyte apoptosis. The present study evaluates the effects of Ang II infusion in rats on podocyte nephrin expression and apoptosis and the molecular mechanisms involved in Ang II-induced proteinuria and mesangial expansion. Methods: Sprague-Dawley rats were randomly assigned to receive either normal saline or Ang II (400 ng.kg(-1).min(-1)) by means of a mini-osmotic pump for variable time periods. Systolic blood pressure and urinary protein and albumin excretion rate measurements were carried out on days 7, 14, 21, and 28. The animals were sacrificed on days 14 and 28 and evaluated for serum creatinine, renal pathological changes, podocyte apoptosis, renal nephrin mRNA, and protein expression. Results: The Ang II-infused rats developed hypertension and proteinuria. On day 14, the Ang II-infused rats showed narrowing of the slit diaphragm, an increase in podocyte nephrin mRNA and protein expression, and alterations in its distribution along the foot processes. On day 28, the Ang II-infused rats demonstrated the presence of apoptotic podocytes and decreased nephrin mRNA and protein expression. There was a negative correlation between nephrin expression and the numbers of apoptotic podocytes (r = -0.63, p < 0.05). Conclusion: These results suggest that changes in nephrin expression may play a role in the pathogenesis of Ang II-induced podocyte apoptosis. Copyright (C) 2008 S. Karger AG, Basel.