辛伐他汀对UUO大鼠肾组织p-Smad2/3表达影响的实验研究

EFFEC OF SIMVASTATIN ON p-SAMD2/3 OF RENAL TISSUE IN UNILATERAL URETERAL OBSTRUCTION RAT

目的观察转化生长因子-β1(transforming growth factor-β1,TGF-β1)/Smads信号传导途径在大鼠肾间质纤维化中的表达及辛伐他汀的干预作用。方法雄性大鼠分为假手术组、模型组和辛伐他汀组。单侧输尿管结扎术(unilateral ureteral obstruction,UUO)建立肾梗阻模型。于术后14d取材。应用HE染色观察肾脏病理变化,免疫组织化学对p-Smad2/3、Ⅰ型胶原蛋白进行定位和半定量观察。同时应用Western blot和反转录聚合酶链反应方法分别检测TGF-β1、p-Smad2/3、Ⅰ型胶原蛋白和(或)mRNA水平表达。生化检测血清胆固醇、甘油三酯水平。结果与假手术组相比,模型组梗阻肾TGF-β1、p-Smad2/3显著升高,同时Ⅰ型胶原蛋白也明显升高。辛伐他汀组均有显著改善。三组间血清胆固醇及甘油三酯水平无显著性差异。结论TGF-β1/Smads信号传导途径在肾间质纤维化形成中可能起着重要促细胞外基质沉积的作用。辛伐他汀可能通过非降脂途径改善肾间质纤维化。

Objective To examine the expression of p-Smad2/3 protein in renal tubulointerstitial fibrosis and simvastatin＇s effect on it. Methods Male SD rats were divided into sham operation,unilateral ureteral obstruction（UUO） and simvastatin groups（ n = 10）. In UUO and simvastatin group UUO was achieved by ligating the left ureter. The rats of simvastatin group was administered with simvastatin by gavage from the day before surgery for 2 weeks. Rats were killed at 14 days. Blood was collected to examing serum creatinine（Scr）, blood urea nitrogen （BUN）, total cholesterol and triglyceride by biochemical method. The protein and/or mRNA of transforming growth factor-β1 （TGF-β1 ）, p-Smad2/3 and collagen I were analyzed by routine immunohistochemical method, western blot and reverse transcription-polymerase chain reaction respectively. At the same time,HE staining was used to examine the area of interstitial fibrosis. Results Compared with sham operation group,TGF-β1 protein/mRNA, p-Smad2/3 and collagen I protein were significantly increased in UUO rats. Immunohistochemistry staining studies indicated that p-Smad2/3 was presented in nuclear of tubular epithelial cell. The expression of TGF-β1 , Smad2/3 and p-Smad2/3 were significantly increased in simvastatin group. Conclusion Smads protein perhaps is the key in the development of tubulointerstitial fibrosis. Simvastatin can decrease renal interstitial fibrosis by TGF-β1 /Smads pathway.