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  

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

作　　者：王艾丽[1] 陈玲玲 胡剑峰[1] 程新耀[1] 

机构地区：[1]武汉大学中南医院超声心动图室 [2]麻城市妇幼保健院儿科

出　　处：《中国临床药理学与治疗学》2007年第9期1058-1061,共4页Chinese Journal of Clinical Pharmacology and Therapeutics

摘　　要：目的:观察阿伐他汀对内皮素-1(endothelin-1ET-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(10-6mol/L)组,阿伐他汀(1.0×10-4mol/L)组,ET-1+阿伐他汀(10-7～10-4mol/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(10-6mol/L)孵育细胞48h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CFsNO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),1.0×10-4mol/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。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.

关 键 词：阿伐他汀 心脏成纤维细胞 内皮素-1 心肌纤维化 

分 类 号：R965.2[医药卫生—药理学]