高脂喂养大鼠肾小管上皮细胞SREBP-1、TGF-β1、α-SMA的表达和细胞外基质沉积  

High fat diet induced the expression of SREBP-1,TGF-β1 and α-SMA in renal tubular cells and extracellular matrix accumulation in Wistar rats

作　　者：郝军[1] 刘淑霞[1] 韦金英[1] 要红叶[1] 段惠军[1] 

机构地区：[1]河北医科大学病理学教研室,石家庄050017

出　　处：《中国应用生理学杂志》2010年第3期307-311,I0001,共6页Chinese Journal of Applied Physiology

基　　金：河北省科技厅资助项目(07276170)

摘　　要：目的:探讨高脂喂养对大鼠肾脏小管上皮细胞SREBP-1、TGF-β1、α-SMA表达和细胞外基质(ECM)的影响。方法:高脂饲料喂养大鼠12周后,油红O检测肾脏脂质沉积,Masson染色检测肾小管间质细胞外基质沉积,免疫组化、Western blot和原位杂交检测SREBP-1、TGF-β1、α-SMA和FN的表达。结果:高脂喂养后大鼠体重明显增加,血糖、甘油三酯和胰岛素均升高,油红O检测显示大鼠肾小管上皮细胞内出现明显脂滴。SREBP-1蛋白和mRNA在肾小管上皮细胞内表达,高脂组高于正常对照组,分别是正常组的1.88倍和1.85倍;TGF-β1和α-SMA也定位于肾小管上皮细胞胞浆并出现上调。Masson染色显示高脂喂养大鼠肾间质ECM沉积增多,纤维粘连蛋白FN检测也显示模型组表达强于对照组。结论:高脂饮食喂养可能通过上调肾脏小管上皮细胞SREBP-1表达使细胞内脂滴沉积,并进一步诱导TGF-β1、α-SMA合成而导致细胞外基质堆积。Objective： To explore the effect of high fat diet on the expression of sterol regulator）, element binding protein-1 （SREBP-1 ）, transforming growth factorbetal （TGF-β1） and a-smooth muscle actin （α-SMA） in renal tubular cells and extracellular matrix accumulation in Wistar rats. Methods： The Wistar rats were treated with high fat diet for 12 weeks and renal lipid deposit was detected by the method of Oil Red O staining. The immunohistochemistry and Western blot were used to investigate the expression of SREBP-1, TGF-β1, α-SMA and fibronectin （FN） protein. The expression of SREBP-1 mRNA was determined with in situ hybridization. Masson staining was for the detection of extracellular matrix （ECM） accumulation. Results： The weight of rats raised by high fat diet increased, in company with the high serum glu- cose, serum triglyceride and serum insulin. The Oil Red O staining revealed that the renal proximal tubular epithelial cells showed significant lipid droplet in high fat diet rats. SREBP-1 protein and mRNA were located in the renal tubular cells and the expressions of high fat diet rats were higher than those of normal control rats. They were respectively 1.88 times and 1.85 times than those of normal control group. TGF-β1 and α-SMA protein were ＇also located in renal tubular cells and high fat diet up-regulated the expression of them. ECM accumulation was detected with Masson staining and the result showed that high fat diet treatment increased interstitial ECM product and FN protein was found high expression. Conclusion： High fat diet may induce lipid droplet deposit in renal tubular cells by up-regulation of the expression of SREBP-1, which causes ECM accumulation by increasing the expression of TGF-β1 and α-SMA.

关 键 词：高脂饮食 肾小管上皮细胞 固醇调节元件结合蛋白-1 转化生长因子-β1 细胞外基质 

分 类 号：R692.6[医药卫生—泌尿科学]