罗格列酮对糖基化终产物诱导的大鼠心肌成纤维细胞及胶原蛋白合成的影响

Effect of rosiglitazone on the myocardial fibroblasts and collagen synthesis in rats induced by advanced glycation end products

目的探讨罗格列酮(RGZ)对糖基化终产物(AGEs)诱导的大鼠心肌成纤维细胞(CFs)及胶原蛋白合成的影响。方法采用胰酶消化法和差速贴壁分离法获取CFs,经AGEs诱导,并给予不同浓度RGZ干预48 h,收集培养上清液,应用四甲基偶氮唑盐比色法(MTT)检测不同浓度RGZ对AGEs作用下的CFs增殖的影响;应用酶联免疫吸附试验(ELISA)检测干预前后胶原蛋白Ⅰ、Ⅲ含量。结果与AGEs 0 mg/L组比较,经不同浓度AGEs诱导后,各组CFs OD490 nm值有所升高,且随AGEs浓度的增加而呈递增趋势;与未干预组比较,各干预组OD490 nm值、胶原蛋白Ⅰ、Ⅲ含量均显著降低,且随RGZ浓度的增加呈递减趋势(P<0.05或P<0.01)。结论 RGZ对AGEs诱导的CFs增殖及促进胶原蛋白Ⅰ、Ⅲ合成作用具有明显的抑制效应,且抑制程度呈浓度依赖性,可有效改善心肌纤维化状态。

Objective To explore the effect of rosiglitazone（ RGZ） on the myocardial fibroblasts（ CFs） and collagen synthesis in rats induced by advanced glycation end products（ AGEs）.Methods CFs were obtained by using trypsin enzyme-digesting method and differential adhesion.After induction by AGEs,different concentrations of RGZ were used to intervene 48 h,and the supernate was collected and cultured. Methyl thiazolyl tetrazolium（ MTT） assay was applied to detect the impact of different concentrations of RGZ on the proliferation of CFs under the action of AGEs,and enzyme-linked immunosorbent assay（ ELISA） was used to detect the contents of collagen Ⅰ and Ⅲbefore and after intervention. Results Compared with AGEs 0 mg / L group,the value of CFs OD490 nmin each group increased,and increased gradually with the concentration of AGEs elevation after induction by different concentrations of AGEs. Compared with non-intervention group,the value of OD490 nmand contents of collagen Ⅰ and Ⅲ in each intervention group decreased significantly,and tended to reduce with the concentration of RGZ elevation（ P〈0. 05 or P〈0. 01）. Conclusion RGZ exerts significantly-inhibitory effects on the proliferation of CFs induced by AGEs and promotion of collagen Ⅰ and Ⅲ synthesis,and this inhibitory degree is concentration-dependent,which can effectively ameliorate the status of myocardial fibrosis.