非诺贝特对高糖培养肾小球系膜细胞胞外基质产生及降解影响  

Effects of fenofibrate on the production and degradation of extracellular matrix of glomerular mesangial cells incubated with high concentration of glucose

作　　者：倪连松[1] 金洁娜[1] 郑景晨[1] 沈飞霞[1] 

机构地区：[1]温州医学院附属第一医院内分泌科,浙江温州325000

出　　处：《温州医学院学报》2009年第6期534-537,共4页Journal of Wenzhou Medical College

基　　金：浙江省留学回国基金资助项目(2005HG01);温州市科技局科研基金资助项目(Y20060066)

摘　　要：目的:探讨非诺贝特对糖尿病肾病的保护机制。方法:大鼠肾小球系膜细胞分别培养在正常糖浓度(5.5 mmol.L-1,对照组)、高糖浓度(25 mmol.L-1,高糖组)及25 mmol.L-1葡萄糖+非诺贝特100μmol.L-1(非诺贝特组)。CCK-8测定系膜细胞增殖;ELISA法检测培养上清液Ⅳ型胶原(Col-Ⅳ)、纤维连接蛋白(FN)、转化生长因子-β1(TGF-β1)、基质金属蛋白酶组织抑制因子-1(TIMP-1);明胶酶谱法检测培养上清基质金属蛋白酶-2,9(MMP-2,9)的活性。结果:高糖组系膜细胞较对照组出现增殖增加,合成基质蛋白Col-Ⅳ,FN增多,MMP-2及MMP-9活性下降,TIMP-1含量增加,TGF-β1分泌增加。与高糖组比较非诺贝特干预后能完全或部分逆转上述变化。结论:非诺贝特能抑制高糖培养的系膜细胞增殖,减少胞外基质合成,增加胞外基质的降解。Objective：To explore the protective mechanism of fenofibrate on diabetic nephropathy.Methods：Rat mesangial cells（MC） were incubated in media containing 5.5 mmol.L-1 glucose（control group）,25 mmol.L-1 high glucose（HG group） and 25 mmol.L-1 glucose＋100μmol.L-1 fenofibrate（FB group）.Cellular proliferation was assessed with CCK-8.Fibronectin（FN）,type Ⅳ collagen（Col-Ⅳ）,transforming growth factor-β1（TGF-β1） and matrix metalloproteinase inhibitor-1（TIMP-1） in supernatant were detected with ELISA method. Activities of matrix metalloproteinase-2,9 （MMP-2,9） in supernatant were detected with gelatinase zymography. Results： Compared with control group, MC in HG group showed a high growth rate and synthesis of Col-Wand FN were increased ; activities of MMP-2 and MMP-9 decreased, and secretion of TGF-β1 and TIMP-1 increased. Compared with HG group, these changes could be fully or partly reversed by fenofibrate treatment. Conclusion： Fenofibrate can inhibit high glucose-induced proliferation of mesangial cells, decrease synthesis of extracellular matrix, and increase degradation of extracellular matrix.

关 键 词：糖尿病肾病 非诺贝特 肾小球系膜细胞 

分 类 号：R965.2[医药卫生—药理学]