摘要
目的观察糖尿病肾脏病大鼠肾脏缺氧诱导因子1α（HIF-1α）表达变化及替米沙坦对其表达的影响。方法18只雄性Wistar大鼠腹腔注射链脲佐菌素（STZ）建立糖尿病。肾脏病模型，随机分为对照组（A组）、糖尿病肾脏病组（B组）和替米沙坦治疗组（C组）。C组给予替米沙坦（5mg·kg^-1·d^-1）灌胃8周。建模成功后第8周末检测各组大鼠24h尿蛋白定量；心脏采血，留取血标本测血糖、血肌酐、血钠、血钾。PAS染色观察肾脏病理改变。免疫组织化学检测各组HIF-1α蛋白在肾脏组织中的表达和分布；RT-PCR检测各组大鼠肾脏组织中HIF-1αmRNA水平。结果①第8周末B组大鼠24h尿蛋白定量较A组显著升高（P〈0．05），C组24h尿蛋白定量较B组明显降低（P〈0．01）。②B组第8周末肾间质损伤指数明显高于A组（P〈0．05），而C组则低于B组（P〈0．05）。③免疫组织化学显示HIF-1α主要表达于肾小管细胞胞浆和胞核，肾小球系膜细胞可见少量表达。与A组比较，B组HIF-1α蛋白及mRNA水平显著升高（P〈0．05），而C组与B组相比显著降低（P〈0．05）。结论糖尿病肾脏病大鼠存在缺氧状态，替米沙坦通过减轻肾小管细胞HIF-1α表达，从而减轻肾脏病变。
Objective To assess the effect of telmisartan on the expression of HIF-1α in the kidneys of diabetic rats. Methods Eighteen male Wistar rats were subjected to subcutaneous injection of streptozotocin （STZ）, and randomly assigned into three groups： control group, diabetic group, telmisartan-treated group. At the end of 8 weeks, urinary proteinuria was measured, rats were sacrificed and blood samples were collected to evaluate biochemical indexes. Renal pathological changes were quantified with renal tubulointerstitial injury index on PAS-stained sections. Immunohistochemistry and RT-PCR were used to detect the expression and distribution of HIF-1α. Results Proteinuria and renal tubulointerstitial injury index in diabetic rats were significantly increased as compared with those in normal rats at the week 8. The protein expression of HIF-1α was down-regulated in the kidneys of telmisartan-treated group as compared with control group, and that in telmisartan-treated group was significantly reduced as compared with diabetic group （P〈0. 05）. Conclusions The hypoxic condition exists in diabetic nephropathy. Telmisartan might improve the hypoxic condition by inhibiting the ex pression of HIF-1α.
出处
《临床肾脏病杂志》
2011年第4期177-180,共4页
Journal Of Clinical Nephrology
基金
国家自然科学基金（30871167,30900688）
