小檗碱对糖尿病肾病大鼠nephrin、podocin和α3β1整合素表达的影响

摘要

目的：观察小檗碱对糖尿病肾病大鼠肾脏足细胞相关蛋白nephrin、podocin和α3β1整合素蛋白表达的影响，探讨小檗碱对糖尿病肾病大鼠肾脏的保护作用及部分机制。方法采用高糖高脂饲料喂养6周，联合低剂量链脲佐菌素诱导糖尿病肾病大鼠模型。随机分为正常对照组、模型组、3个不同剂量(50、100和200 mg·kg-1)小檗碱给药组和依那普利阳性药对照组(1 mg·kg-1)。分别采用免疫组织化学法，油镜(×1000倍)和高倍镜(×400倍)和 Western blot法，观察和检测肾脏足细胞相关蛋白 nephrin、podocin 及α3β1整合素的分布和表达水平。结果足细胞相关蛋白nephrin、podocin及α3β1整合素蛋白主要分布于足细胞，但分布位置略有差异；与正常对照组相比，模型组大鼠的足细胞相关蛋白nephrin、podocin及α3β1整合素的表达水平明显降低；与模型组相比，小檗碱(100和200 mg · kg-1)给药组明显改善糖尿病肾病大鼠肾脏形态学异常，上调足细胞相关蛋白nephrin、podocin及α3β1整合素的表达水平。结论小檗碱可以缓解糖尿病肾病大鼠肾脏病理异常改变及蛋白尿的产生，这可能与其上调足细胞相关蛋白nephrin、podocin及整合素α3β1的表达相关。%Aim To investigate the effect of berberine on the expression of nephrin, podocin and intergrinα3β1 in diabetic nephropathy ( DN ) rat model, and further probe in to the renoprotective effects of berber-ine and its potential mechanisms. Methods The rat model of DN was induced by intraperitoneal injection of streptozotocin ( STZ ) after fed with high-sugar and high-fat diet for six weeks. The rats were assigned into 6 groups randomly: normal control group, DN model group, BBR (50,100 and 200 mg·kg-1 ) treatment group and enalaprilat positive control group ( 1 mg · kg-1 ) . The distribution and expression of kidney podocyte related proteins nephrin, podocin and interg-rinα3β1 were detected by immunohistochemical meth-od following electron microscopy observation ( × 1000 ) and high magnification observation( × 400) and West-ern blot. Results The podocyte related protein neph-rin, podocin and intergrin α3β1 were mainly distribu-ted in podocyte, but slightly different. Compared with normal control group, the expresion of podocyte related protein nephrin, podocin and intergrin α3β1 was de-creased obviously; compared with model group, BBR (100 and 200 mg·kg-1 ) treatment group could sig-nificantly suppress the abnormalities of pathological changes of the kidney and upregulate the expression levels of podocyte specific protein nephrin, podocin and intergrin α3β1 in the kidney of diabetic rats with nephropathy. Conclusions Berberine could alleviate the abnormalities of kidney pathological changes and proteinuria production in the DN model rats, which may be related to the upregulation of the expression of the podocyte proteins nephrin, podocin and intergrinα3β1.