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目的 :观察非选择性内皮素受体拮抗剂波生坦 (Bosentan)对糖尿病SD大鼠的肾脏保护作用。 方法 :设糖尿病非治疗组 (DM组 )、糖尿病Bosentan治疗组 (DM B组 )及正常对照组 (SD组 ) ,每组 6只大鼠。予SD大鼠一次性腹腔注射链脲佐菌素 6 5mg/kg ,诱导建立糖尿病模型。在DM B组中 ,予大鼠Bosentan 10 0mg/ (kg·d)灌胃 ,持续 4周。 4周后观察各组大鼠体重、肾重、平均动脉压、2 4h尿蛋白、肌酐清除率 (Ccr)等生化指标 ,比较各组大鼠血循环及肾脏内皮素含量 ,以及采用Westernblot方法观察各组大鼠肾脏转化生长因子β1(TGF β1)的表达 ,并用免疫组织化学方法观察肾脏细胞外基质Ⅳ型胶原、Laminin以及TGF β1表达。 结果 :DM组大鼠 2 4h尿蛋白排出量、Ccr与SD大鼠对照组相比均明显增加 (均为P <0 0 0 1)。Bosentan使糖尿病大鼠的尿蛋白与Ccr正常化 (与正常组相比 ,均为P >0 0 5 )。Westernblot结果显示肾脏TGF β1蛋白水平在DM组大鼠明显升高 (P <0 0 1) ,为SD组大鼠的 1 97倍 ,Bosentan可使其抑制 5 3 5 % ,与DM组差别有极显著意义 (P <0 0 1)。免疫组织化学结果表明 ,在DM组大鼠中 ,肾小球、肾小管基膜及肾小球系膜区Ⅳ型胶原与Laminin的表达明显增加 ,肾小管间质的TGF β1表达也显著增加。Bosentan?
Objective: To observe the protective effect of Bosentan, a nonselective endothelin receptor antagonist, on the kidney of diabetic SD rats. Methods: A total of 6 rats in each group were divided into two groups: untreated diabetic group (DM group), diabetic Bosentan treated group (DM group B) and normal control group (SD group). Sprague-Dawley rats were given intraperitoneal injection of streptozotocin 6 5mg / kg to induce the establishment of diabetic model. In DM group B, rats were given Bosentan 10 0 mg / (kg · d) orally for 4 weeks. After 4 weeks, the body weight, kidney weight, mean arterial pressure, 24h urinary protein and creatinine clearance (Ccr) and other biochemical indicators were observed. The blood circulation and renal endothelin levels of the rats in each group were compared. Western blotting The expression of transforming growth factor-β1 (TGF-β1) in the kidney of rats was observed. The expressions of type Ⅳ collagen, Laminin and TGFβ1 in renal extracellular matrix were observed by immunohistochemistry. Results: Urine protein excretion of 24 h in DM group was significantly higher than that in control group (all P <0.01 01). Bosentan normalizes urine protein and Ccr in diabetic rats (all P> 0.05). The result of Western blot showed that the level of TGF-β1 protein in kidney of diabetic rats was significantly higher than that of DM rats (P <0.01), which was 97 times higher than that of SD rats and decreased to 535% with Bosentan Significant (P <0.01). The results of immunohistochemistry showed that the expressions of type Ⅳ collagen and Laminin in glomeruli, tubular basement membrane and glomerular mesangial area were significantly increased and the expression of TGFβ1 in tubulointerstitial was also significantly increased in DM group rats. Bosentan?