阿伐他汀对内皮素-1诱导的新生大鼠心肌成纤维细胞增殖和胶原合成的影响

目的观察阿伐他汀对内皮素-1(endothelin-1 ET-1)诱导的心脏成纤维细胞(cardiac fibroblast,CFs)增殖和胶原合成的影响及可能机制.方法经差速贴壁法培养新生大鼠CFs,随机分为4组空白对照组,ET-1(10-6 mol/L)组,阿伐他汀(1.0×10-4 mol/L)组,ET-1 阿伐他汀(10-7～10-4 mol/L)组.采用四氮唑盐(MTT)比色法测定细胞数目,流式细胞仪(FCM)检测细胞周期,液体闪烁计数仪测定[3H]-脯氨酸掺入率,硝酸还原酶法测定上清液中NO含量.结果与空白对照组比较,ET-1(10-6 mol/L) 孵育细胞 48 h 后可显著增加MTT比色法测定的CFs吸光度A490值和[3H]-Pro掺入率,降低CFs生成NO的量(P＜0.01);随着阿伐他汀浓度的增高,CFs的A490值和[3H]-Pro掺入率呈明显的递减趋势(P＜0.01),促进CFs NO的生成(P＜0.01);细胞周期分析表明,与空白对照组比较ET-1能显著提高S期细胞百分率(P＜0.01),1.0×10-4 mol/L 阿伐他汀抑制ET-1诱导S期细胞百分率上升(P＜0.01).结论阿伐他汀呈浓度依赖性抑制ET-1诱导的CFs增殖和胶原合成,该作用可能与NO生成有关.

Effects of atorvastatin on the proliferation and collagen synthesis of cardiac fibroblasts induced by endothelin-1

AIM:To investigate the effects of atorvastatin on the proliferation and collagen synthesis of cardiac fibroblasts(CFs) induced by endothelin-1(ET-1).METHODS:Neonatal rat cardiac fibroblasts were randomly divided into 4 groups:control,ET-1,Atorvastatin,ET-1 atorvastatin(10-7-10-4 mol/L).CFs number was measured by MTT assay.Cell cycle distribution was determined with flow cytometer(FCM).[3H]-Proline uptake was evaluated by scinillation counting.Nitric Oxide(NO) was measured by chromatometry.RESULTS:10-6 mol/L ET-1 significantly increased the A490 value and [3H]-Pro incorporation,and decreased the secretion of NO compared with the control group(P<0.01).10-7-10-4 mol/L atorvastatin inhibited the above effects of ET-1 on CFs in a concentration-dependent manner(P<0.01 vs ET-1).In the ET-1 group,Phase S cell percentage was higher than that of contol,which was inhibited by atorvastatin(P<0.01 vs ET-1 and control).CONCLUSION:Atorvastatin dose-dependently inhibits the proliferation and collagen synthesis of cardiac fibroblasts induced by endothelin-1,which may be partially mediated by NO.