脂质与糖尿病大鼠肾小球TGF-β/Smad信号通路的关系

Lipid activates TGF-β/Smad signaling pathway in glomeruli of diabetic rats

目的探讨脂质对糖尿病大鼠肾小球TGF-β/Smad信号通路的影响。方法糖尿病大鼠随机分成普通饲料组,高脂饲料组、高脂饲料加辛伐他汀干预组(辛伐他汀组)和正常对照组。16周后,采用RT-PCR、免疫组化和Western印迹法检测大鼠肾小球转化生长因子β1(TGF-β1)、转化生长因子II型受体(TβRII)、Ⅵ型胶原(ColⅥ)mRNA和蛋白和磷酸化Smad2(p-Smad2)表达的变化。结果与正常对照组比较,普通饲料组、高脂饲料组、辛伐他汀组肾小球TGF-β1、TβRII、ColⅥmR-NA和蛋白及p-Smad2表达均上调,高脂饲料组上调最为明显;与高脂饲料组比较,辛伐他汀组TGF-β1、TβRII、ColⅥ和p-Smad2表达明显下调。结论脂质通过激活TGF-β/Smad信号通路,加剧糖尿病肾脏病变;辛伐他汀抑制TGF-β/Smad通路的激活,延缓糖尿病肾病的进展。

Objective To investigate the effects of lipid on TGF-β/Smad signaling pathway in glomeruli of diabetic rats. Methods STZ-induced SD rats were assigned to diabetic rats with common diet ingestion （CD） group, diabetic rats with high fat diet ingestion group（FD）, diabetic rats with high fat diet ingestion and simvastatin（4mg/kg/d） treatment （FS） group, in addition to normal control（C） group. RT-PCR, immunohistochemistry, and Western blot were employed to examine the changes in the mRNA and protein expressions of TGF-β1, TβRⅡ, p-Smad2 and ColVI in glomeruli of these rats after 16 weeks. Results In comparison with C group, the mRNA and/or protein expressions of TGF-β1 ,TβRⅡ,p-Smad2 and ColⅥ in glomeruli of CD group, FD group and FS group were significantly increased （P〈0.05）, whereas the increases in the expression of mRNA and protein in FD group were the most prominent. Simvastatin could markedly decrease the mRNA and/or protein expressions of TGF-β1 ,TβRⅡ,p-Smad2 and ColVI in glomeruli of FS group （P〈0.05）. Conclusions Lipid may play a key role in development of diabetic nephropathy by activating the TGF-β/Smad signaling pathway. Simvastatin can inhibit the over-activating of this pathway, which may have benefits in diabetic nephropathy.