辛伐他汀和西拉普利对人肾小球系膜细胞TGF-β_1和IGF-Ⅰ表达的影响

Effects of simvastatin and cilazapril on expressions of transforming growth factor-β_1 and insulin-like growth factor-Ⅰ in cultured human glomerular mesangial cells

目的 探讨辛伐他汀和西拉普利对人肾小球系膜细胞转化生长因子 β1(TGF β1)和胰岛素样生长因子Ⅰ (IGF Ⅰ )表达的影响。方法 体外培养人胎肾小球系膜细胞 ,在低糖 (5 .6mmol/L)和高糖 (3 0mmol/L)环境下 ,加入辛伐他汀 (10 μmol/L)、西拉普利 (10 μmol/L)及辛伐他汀 +西拉普利培养 48h后 ,分别测定细胞上清液中TGF β1、纤维连接蛋白、层粘连蛋白和Ⅳ型胶原 (酶免法和放免法 )浓度及系膜细胞TGF β1和IGF ⅠmRNA表达水平 (RT PCR法 )。结果 与低糖比较 ,高糖环境中系膜细胞过度增殖 ,TGF β1和IGF ⅠmRNA表达明显增高 ,细胞上清液中TGF β1、纤维连接蛋白、层粘连蛋白和Ⅳ型胶原含量也显著升高。加入辛伐他汀和西拉普利后 ,高糖环境下系膜细胞TGF β1和IGF ⅠmRNA的表达明显降低 ,细胞上清液中TGF β1和基质蛋白含量也亦显著下降。合用辛伐他汀和西拉普利对系膜细胞TGF β1表达的抑制作用较单独用上述两药更强。结论 高糖可促进系膜细胞TGF β1和IGF Ⅰ的表达 ,辛伐他汀和西拉普利可一定程度逆转高糖环境中系膜细胞TGF β1和IGF Ⅰ的过度表达 ,并降低细胞上清液中TGF β1和基质蛋白的含量。

Objective To explore the effects of simvastatin and cilazapril on the expression of transforming growth factor-β_1 (TGF-β_1) and insulin-like growth factor-Ⅰ (IGF-Ⅰ) in the cultured human glomerular mesangial cells. Methods Human embryo glomerular mesangial cells were cultured in media with lower (5.6 mmol/L) or higher (30 mmol/L) glucose concentrations. Forty-eighthoursafteraddingsimvastatin(10 μmol/L)and/or cilazapril (10 μmol/L) to the cultured media, the concentrations of TGF-β_1, fibronection, laminin, type Ⅳ collagen proteins in the supernatant of cultured mesangial cells were determined by ELISA and radioimmunoassay and the expressions of TGF-β_1 and IGF-Ⅰ mRNA in cultured mesangial cells were also evaluated by RT-PCR. Results Compared with lower glucose control, the mesangial cells in the medium with higher glucose concentration showed excessive proliferation and higher expressions of TGF-β_1 and IGF-Ⅰ mRNA, and the levels of TGF-β_1, fibronection, laminin, and type Ⅳ collagen in the supernatant were also significantly increased. The expressions of TGF-β_1 and IGF-Ⅰ mRNA in the mesangial cells and the concentrations of TGF-β_1 and the extracellular matrix (ECM) proteins in the supernatant were all decreased after addition of simvastatin and cilazapril. Combination of simvastatin and cilazapril resulted in more profound suppressive effect on the expression of TGF-β_1 mRNA than either of them alone. Conclusion High concentration of glucose stimulates the cultured human mesangial cells excessively to express the TGF-β_1, IGF-Ⅰ and ECM proteins, and the high glucose-induced changes are suppressed by either simvastatin, cilazapril alone or combined treatment.