食饵性高脂血症对糖尿病大鼠肾脏TGF-β/Smad信号通路的激活  

Hyperlipidemia induced by high fat diet ingestion activates TGF-β/Smad signaling pathway in the kidney of diabetic rats

作　　者：陈卓雄[1] 谢晓云[1] 喻日成[2] 张军[1] 雷闽湘[1] 

机构地区：[1]中南大学湘雅医院内分泌科,长沙410008 [2]贵州省人民医院内分泌科,贵阳550002

出　　处：《中南大学学报（医学版）》2008年第10期906-912,共7页Journal of Central South University ：Medical Science

基　　金：湖南省自然科学基金(03JJY4025)~~

摘　　要：目的:观察食饵性高脂血症对链脲佐菌素(STZ)诱导的糖尿病SD大鼠肾脏皮质TGF-β/Smad信号通路的影响,探讨脂质对糖尿病肾脏损伤的作用机制。方法:STZ腹腔注射法诱导SD大鼠糖尿病成模,正常饮食和高脂饮食分别喂养糖尿病大鼠和非糖尿病大鼠16周。半定量逆转录PCR(RT-PCR)检测各组大鼠肾脏皮质转化生长因子β1(TGF-β1)、转化生长因子Ⅱ型受体(TβRⅡ)和Ⅳ型胶原(Col-Ⅳ)mRNA表达的变化;免疫组织化学染色检测各组大鼠肾小球TβRⅡ和磷酸化Smad2蛋白(p-Smad2)的表达和定位;Western印迹检测各组大鼠肾皮质TGF-β1和Col-Ⅳ蛋白表达变化。结果:高脂喂养上调糖尿病SD大鼠肾脏皮质TGF-β1,TβRⅡ,p-Smad2和Col-Ⅳ蛋白和mRNA表达水平,高脂喂养对非糖尿病SD大鼠肾脏皮质TGF-β1,TβRⅡ,p-Smad2和Col-ⅣmRNA和/或蛋白表达无明显影响。结论:高脂血症可能通过激活TGF-β/Smad信号通路,导致糖尿病肾脏损害。Objective To investigate the effect of diet-induced hyperlipidemia on TGF-β/ Smad signaling pathway in the kidney of diabetic rats, and to explore the mechanism by which hyperlipidemia leads to renal injury in diabetes. Methods Diabetic rats and non-diabetic rats were fed with normal fat diet and high fat diet for 16 weeks, respectively. The expressions of TGF-β1 , TβR Ⅱ , and Col-Ⅳ mRNA in the renal cortex were examined by reverse transcriptase-PCR ,TβR Ⅱ and p-Smad staining in glomerular cells were detected by immunohistochemical staining, and the expression of TGF-β1 and Col-Ⅳ protein was determined by Western blot. Results Diet-induced hyperlipidemia up-regulated the levels of TGF-β1 , TβR Ⅱ , p-Smad, and Col-Ⅳ protein and mRNA in the renal cortex of diabetic rats compared with those of non-diabetic rats. However, feeding high fat diet to non-diabetic rats had no influence on the expression of TGF-β1 , TβR Ⅱ , p-Smad2, and Col-Ⅳ in the renal cortex. Conclusion Hyperlipidemia induced by high fat diet ingestion leads to renal injury in diabetic rats through activating TGF-β1 /Smad signaling pathway.

关 键 词：脂质 糖尿病肾病 细胞外基质 转化生长因子-Β1 SMAD蛋白 

分 类 号：R587.2[医药卫生—内分泌]