奥帕曲拉对内皮素-1诱导的心脏成纤维细胞增殖的影响  

EFFECTS OF OMAPATRILAT ON ENDOTHELIN-1-INDUCED PROLIFERATION AND SYNTHESIS OF CARDIAC FIBROBLASTS

作　　者：郑亚萍[1] 徐江[1] 赵艳峰[1] 

机构地区：[1]武汉大学医学院生理学系,湖北武汉430071

出　　处：《中国应用生理学杂志》2007年第4期415-418,共4页Chinese Journal of Applied Physiology

摘　　要：目的:探讨奥帕曲拉(omapatrilat,OMA)对内皮素-1(ET-1)诱导的心脏成纤维细胞(CFs)增殖的干预作用及可能机制。方法:经差速贴壁法培养的新生大鼠CFs,随机分为7组:对照组,ET-1组,OMA组,ET-1+OMA10-9mol/L组,ET-1+OMA10-8mol/L,ET-1+OMA10-7mol/L组,ET-1+OMA10-6mol/L组。采用四氮唑盐(MTT)比色法测定CFs数目,流式细胞分析仪(FCM)检测CFs细胞周期,液体闪烁计数仪测定CFs3H-脯氨酸掺入率,硝酸还原酶法测定细胞培养上清液中NO含量。结果:与对照组相比,10-7mol/LET-1能显著增加CFs的吸光度A490值及[3H]-Pro掺入率,降低CFs生成NO的量(均P<0.01),10-9-10-6mol/LOMA呈浓度依赖性的降低ET-1诱导的A490值和[3H]-Pro掺入率升高(均P<0.01),促进CFsNO的生成(均P<0.05);细胞周期分析表明ET-1能显著提高S期细胞百分率(P<0.01),10-7mol/LOMA抑制ET-1诱导S期细胞百分率上升(P<0.01)。结论:OMA对ET-1诱导的CFs增殖及胶原合成有抑制作用,该作用可能和NO生成有关。To investigate the effects of omapatrilat（OMA） on endothelin-1-induced proliferation of cardiac fibroblasts（CFs）. Methods： Isolated and cultured CFs from neonatal Sprague-Dawley rats（SD） were randomly divided into 7 groups： （1）Control, （2）ET-1, （3）OMA, （4）ET- 1 ＋ OMA 10^- 9 mol/L,（5）ET- 1 ＋ OMA 10^ -8 mol/L, （6）ET- 1 ＋ OMA 10^- 7mol/L and （7）ET- 1 ＋ OMA 10^- 6 mol/ L. CFs were counted by MTT assay. Cell cycle distribution was determined with a flow cytometer（FCM）. [^3H]-Proline incorpora- tion was evaluated by scintillation counting. Nitric oxide（NO） was measured by colorimetry. Results： 10^-7mol/L ET-1 significantly increased A490 value and [^3H]-Pro incorporation and decreased NO secretion compared with the control group（ P 〈 0.01 ）. 10^-9 - 10^-6 mol/L OMA inhibited the effects of ET-1 on CFs in a concentration-dependent manner （ P 〈 0.01 vs ET-1 ）. In the ET-1 group, the percentage of cells in the S phase was higher than control, which was inhibited by 10^-6 mol/L OMA（P〈0.01 vs ET-1 and control）. Conclusion： OMA can restrain the proliferation and collagen synthesis of cardiac fibroblasts induced by endothelin-1, and this effect may be partially mediated by NO.

关 键 词：内皮素-1 心脏成纤维细胞 奥帕曲拉 缓激肽 一氧化氮 

分 类 号：R331.3[医药卫生—人体生理学]