罗格列酮对高糖培养肾小球系膜细胞胞外基质产生及降解的影响

目的: 探讨罗格列酮(rosiglitazone maleate)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) ,高糖浓度(25 mmol/L )及25 mmol/L 葡萄糖+20μmol/L 罗格列酮的培养液中。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液基质金属蛋白酶-2,9(MMP-2, 9) 的活性。结果: 高糖组系膜细胞较正常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, 罗格列酮干预后能逆转上述变化。结论: 罗格列酮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。

Effects of rosiglitazone on the production and degradation of extracel-lular matrix of glomerular mesangial cells incubated with high concen-tration of glucose

AIM: To investigate the protection mechanisms of rosiglitazone on diabetic nephropathy. METHODS: Rat mesangial cells(MC) were incubated in media containing 5.5 mmol/L normal control glu-cose, 25 mmol/L high concentration glucose, 25 mmol/L glucose +20 μmol/L rosiglitazone maleate. Cells proliferation were assessed by CCK-8.Synthesis of fibronectin (FN) , type Ⅳ collagen (Col-Ⅳ) , transforming growth factor-β₁ (TGF-β₁ ) and matrix met-alloproteinase inhibitor-1(TIMP-1) in supernatant were determined by ELISA method, the activities of matrix metalloproteinase-2, 9 (MMP-2, 9) in supernatant were determined by gelatinase zymography .RESULTS: Compared with control group, MC cultured with high concentration glucose showed a high growth rate and in-creased synthesis of Col-Ⅳand FN, decreased the activities of MMP-2 and MMP-9, and increased secretion of TGF-β₁ and TIMP-1.Compared with high glucose group, these changes could be reversed by rosiglitazone intervention .CONCLUSION: Rosiglitazone could in-hibit high concentration glucose-induced proliferation of mesangial cells, decrease synthesis of extracellular matrix, and increase degradation of extracellular matrix.