Department of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing, Jiangsu 210009, China.
Chin Med J (Engl). 2012 Mar;125(5):888-93.
Integrin-linked kinase (ILK) dysregulation is involved in the progression of diabetic nephropathy (DN). The aim of this study was to investigate the effects of angiotensin II receptor blocker (ARB), irbesartan, on ILK expression and podocyte injury in DN.
DN was induced by the combined feeding of high-sucrose, high-fat diet and intra-peritoneal injection of low dose of streptozotocin (35 mg/kg) in spontaneously hypertensive rats. Diabetic rats were treated with irbesartan (50 mg×kg(-1)×d(-1)) by gavage for 8 weeks. The renal morphologic changes and podocyte injury were investigated by light and electron microscopy, and the ILK expression was evaluated by real-time RT-PCR and Western blotting analysis.
Diabetic rats exhibited with the similar clinical feature of type 2 DN. Morphologically, they were characterized by expansion of mesangial matrix, loss of podocyte and podocyte injury. Impressively, compared to controls, the ILK expression in diabetic rats were upregulated, which were positively correlated with both podocyte injury and albuminuria. Irbesartan significantly prevented ILK overexpression, along with the amelioration of podocyte injury and albuminuria.
ILK plays an important role in mediating podocyte injury in DN; irbesartan inhibits ILK upregulation and attenuates podocyte injury, which might offer a new insight into the role of ARB in preventing DN progression.
整合素连接激酶（ILK）失调参与了糖尿病肾病（DN）的进展。本研究旨在探讨血管紧张素Ⅱ受体阻滞剂（ARB）厄贝沙坦对 DN 中 ILK 表达和足细胞损伤的影响。
通过给予自发性高血压大鼠高蔗糖、高脂肪饮食联合腹腔注射小剂量链脲佐菌素（35mg/kg）诱导 DN。糖尿病大鼠给予厄贝沙坦（50mg×kg（-1）×d（-1））灌胃 8 周。通过光镜和电镜观察肾脏形态变化和足细胞损伤，实时 RT-PCR 和 Western blot 分析评估 ILK 表达。
糖尿病大鼠表现出与 2 型 DN 相似的临床特征。形态上，它们的特点是系膜基质扩张、足细胞丢失和足细胞损伤。令人印象深刻的是，与对照组相比，糖尿病大鼠的 ILK 表达上调，与足细胞损伤和蛋白尿呈正相关。厄贝沙坦显著抑制了 ILK 的过度表达，同时改善了足细胞损伤和蛋白尿。
ILK 在介导 DN 中的足细胞损伤中起重要作用；厄贝沙坦抑制 ILK 的上调，减轻足细胞损伤，这可能为 ARB 在预防 DN 进展中的作用提供新的见解。
