Effects of Angiotensin Receptor Blocker on Phenotypic Alterations of Podocytes in Early Diabetic Nephropathy
Effects of Angiotensin Receptor Blocker on Phenotypic Alterations of Podocytes in Early Diabetic Nephropathy
复制标题
血管紧张素受体阻滞剂对早期糖尿病肾病足细胞表型改变的影响
DOI：
10.1097/maj.0b013e3182010da9
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发表时间：
2011-03-01
影响因子：
3.1
通讯作者：
Liu, Bi-Cheng
中科院分区：
文献类型：
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作者：
Dai, Hou-Yong;Zheng, Min;Liu, Bi-Cheng
背景：新的证据表明足细胞损伤是糖尿病肾病（DN）阶段的关键事件，血管紧张素II参与了这一过程。在这项研究中，作者研究了血管紧张素受体阻滞剂厄贝沙坦对实验性DN足细胞表型改变的影响。方法：采用高糖高脂饮食联合腹腔注射小剂量链脲佐菌素（35 mg/kg）建立自发性高血压大鼠DN模型。糖尿病大鼠灌胃厄贝沙坦（50 mg/kg/d）8周。非糖尿病血压正常的Wistar-Kyoto大鼠，具有相同的遗传背景的自发性高血压大鼠，作为对照。光镜和电镜观察肾组织学变化。实时荧光定量RT-PCR和Western blotting检测上皮细胞nephrin和间质细胞结蛋白。结果：与对照组相比，糖尿病大鼠肾小球系膜基质沉积，肾小球基底膜增厚，蛋白尿，足细胞减少，足突消失。此外，nephrin的表达显着减少，而结蛋白增加。厄贝沙坦治疗不仅降低了血压和蛋白尿，而且减轻了足细胞丢失，维持了nephrin表达并抑制了结蛋白表达。结论：厄贝沙坦早期干预可减轻足细胞损伤，改善足细胞表型改变，为早期应用血管紧张素受体阻滞剂预防DN的发生提供了新的思路。
Background:Emerging evidence suggests that podocyte injury is a crucial event in the stage of diabetic nephropathy (DN), a process in which angiotensin II is implicated. In this study, the authors investigated the influence of irbesartan, an angiotensin receptor blocker, on the phenotypic alterations of podocytes in experimental DN. Methods:DN was induced by combination of high-sucrose, high-fat diet and intraperitoneal injection of low dose of streptozotocin (35 mg/kg) in spontaneously hypertensive rats. Diabetic rats were treated with irbesartan (50 mg/kg/d) by gavage for 8 weeks. Nondiabetic normotensive Wistar-Kyoto rats, which have the same genetic background as spontaneously hypertensive rat, were used as controls. The renal histological changes were investigated by light and electron microscopy. The epithelial marker of nephrin and mesenchymal marker of desmin were detected by real-time reverse transcriptase-polymerase chain reaction and Western blotting. Results:Compared with controls, diabetic rats were associated with mesangial matrix deposition, thickening of glomerular basement membrane, albuminuria, loss of podocytes and effacement of foot processes. Furthermore, the expression of nephrin was significantly reduced whereas desmin was increased. Irbesartan treatment not only lowered blood pressure and albuminuria but also attenuated podocyte loss, maintenance of nephrin expression and inhibition of desmin expression. Conclusions:This study demonstrates that early irbesartan intervention attenuates the podocyte damage and ameliorates phenotypic alterations of podocytes, which provides a novel insight for the early application of angiotensin receptor blocker to prevent the development of DN.