依那普利拉对新生大鼠心肌成纤维细胞增殖及NOS/NO系统的影响

目的：观察血管紧张素Ⅰ转换酶抑制剂（ACEI）依那普利拉（Ena）对血管紧张素Ⅱ（AngⅡ）诱导的新生大鼠心肌成纤维细胞（CFb）增殖及其对一氧化氮合酶/一氧化氮系统（NOS/NO）的影响，探讨Ena抑制心肌成纤维细胞增殖的初步机制。方法：培养的新生Wistar大鼠CFb，分为对照组、模型组和3个剂量Ena给药组，采用胰酶消化、差速贴壁法培养CFb，四氮唑盐（MTT）比色法检测细胞增殖；流式细胞仪测定细胞周期；硝酸还原酶法和分光光度法分别测定不同干预条件下CFb培养液中NOS/NO活性。结果：Ena能够显著抑制AngⅡ诱导的CFb增殖，Ena 3个剂量组作用24、48和72 h时间点的MTT值与模型组比较，差异具有显著性（P<0.05或P<0.01）；与模型组比较，Ena能提高细胞周期G₀/G₁百分率，降低S期百分率，差异具有显著性（P<0.05或P<0.01）；与模型组比较， Ena能够提高CFb上清液中NOS/NO 水平，且随着用药剂量和作用时间增加，NOS活性和NO含量明显升高（P<0.05或P<0.01）。结论：Ena抗CFb增殖的作用与提高CFb NOS/NO 系统活性，拮抗AngⅡ的生物效应有关。

Effects of Enalaprilat on proliferation and nitric oxide synthase-nitric oxide system of neonatal rat cardiac fibroblasts

Objective To investigate the effects of angiotensin Ⅰ-converting enzyme inhibitor Enalaprilat(Ena) on proliferation and nitric oxide synthase-nitric oxide system of neonatal rat cardiac fibroblasts(CFb)and to probe its anticardiac fibrosis mechanism.Methods The cultured neonatal Wistar rat CFb were divided into control group,model group and three doses of Ena groups.CFb were isolated by trypsin digestion method.MTT colorimetric assay was adopted to evaluate cell proliferation,flow cytometry was used to measure cell cycle,nitric acid reductase method and spectrophotometry were used to detect the NO contents and NOS activity respectively with Ena.Results Ena could inhibit CFb proliferation induced by AngⅡ,there were significant differences of MTT values between model group and Ena groups after treated for 24,48 and 72 h(P<0.05 or P<0.01);compared with model group,Ena increased the percentage of cells at phase G0/G1,and decreased the percentage of cells at phase S,there were significant differences(P<0.05 or P<0.01);compared with model group,Ena increased the level of NOs/NO of CFb supernatant,the NOS activity and NO content increased significantly with the increasing of dose and time(P<0.05 or P<0.01).Conclusion The anti-proliferative effects of Ena on CFb can be attributed to enhancing nitric oxide synthase-nitric oxide system of cardiac fibroblasts and accordingly increasing NO level.