SREBP-1在1型糖尿病大鼠肾脏的表达和胰岛素的干预性研究  

Expression of SREBP-1 in kidney of type 1 diabetic rats and insulin intervention

作　　者：郝军[1] 朱琳[2] 戎赞华[1] 段惠军[1] 

机构地区：[1]河北医科大学病理学教研室,河北石家庄050017 [2]河北医科大学附属三院肌电图室,河北石家庄050051

出　　处：《中国药理学通报》2009年第1期95-99,共5页Chinese Pharmacological Bulletin

基　　金：河北省科技厅资助项目(No07276170)

摘　　要：目的探讨1型糖尿病大鼠肾脏脂质沉积和固醇调节元件结合蛋白-1(sterol regulatory element binding protein-1,SREBP-1)的表达以及胰岛素处理的影响。方法以Wistar大鼠建立链脲佐菌素1型糖尿病模型并随机分为正常对照组,糖尿病模型组和胰岛素处理组。喂养2 wk后处死,测定肾皮质组织甘油三酯含量,油红O染色检测脂质沉积的部位;免疫组织化学、Western blot和原位杂交检测肾脏SREBP-1表达。结果与正常对照组相比,1型糖尿病大鼠肾脏甘油三酯含量明显升高,油红O检测示脂质沉积定位于肾近曲小管上皮细胞,肾小球内未见着色。胰岛素处理明显降低了甘油三酯含量,和糖尿病模型组相比差异有统计学意义。免疫组织化学检测SREBP-1定位于大鼠肾脏近曲小管上皮细胞胞质,糖尿病组表达量明显高于正常组和胰岛素处理组。Western blot证实了SREBP-1蛋白前体片段和成熟片段在糖尿病组的高表达,前体片段积分光密度比值为0.673±0.027,成熟片段为0.670±0.028,分别是正常组的1.86倍和1.77倍;胰岛素处理后SREBP-1蛋白前体片段表达下降了52.8%,成熟片段表达量下降了30.9%。原位杂交结果证实SREBP-1 mRNA定位于近曲小管上皮细胞胞质,糖尿病组表达明显升高,与正常对照组相比差异有统计学意义(P<0.01);胰岛素处理后其表达明显下降。结论1型糖尿病大鼠肾近曲小管上皮细胞SREBP-1 mRNA和蛋白表达升高可能参与了肾脏脂质沉积,胰岛素处理可有效降低SREBP-1mRNA和蛋白表达。Aim To investigate the expression of SREBP-1 （sterol regulatory element binding protein-1 ） in the kidney of type 1 diabetic rats and the effect of insulin. Methods The type 1 diabetic models were induced by high dose of STZ and rats were randomly divided into three groups： normal control group, diabetes control group and insulin treated group. At the 2nd week end, the triglyceride （TG） content in the kidney of experimental rats was measured by the assay kit and oil Red 0 staining. Furthermore, the expression of SREBP-1 protein was detected by the methods of Western blot and immunohistochemistry, The analysis of SREBP-1 mRNA was performed by in situ hybridization. Results Compared with the control group, the type 1 diabetic rats＇ renal triglyceride content markedly increased, and the result of Oil Red O showed that lipid deposited in the renal tubular epithelium. Triglyceride content markedly decreased after insulin treatment. The difference had statistic meaning, compared with the diabetes model group. Immunohistochemistry presented the results that SREBP-1 protein was up-regulated in renal tubular epithelium of diabetic rats and in- sulin treatment suppressed the increasing. The results of western blot showed that the precursor and mature segments of SREBP-1 protein in kidney of diabetes group rats were about 1.86 times and 1.77 times respectively of that of normal control group rats. In situ hybridization confirmed the increasing of SREBP-1 mRNA in renal tubular epithelium in diabetic rats. The effect of insulin treatment on SREBP-1 expression was detected by the methods of Western blot and in situ hybridization and it was found that the SREBP-1 mRNA and protein of kidney were down-regulated. Compared with the normal group, the difference has statistic meaning（ P 〈 0.01 ） ;the expression decreased marked- ly after the insulin treatment. Conclusion The above results suggests that altered SREBP-1 may play an important role in the pathogenesis of renal lipid accumulation in type 1 diabetic rats

关 键 词：糖尿病 脂质沉积 固醇调节元件结合蛋白-1 胰岛素 

分 类 号：R-332[医药卫生] R322.61