阿司匹林抑制内皮素-1诱导的大鼠心脏成纤维细胞增殖

目的 探讨阿司匹林（Aspirin）对内皮素-1(ET-1)诱导的大鼠心脏成纤维细胞（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、阿司匹林组、ET-1+ 阿司匹林1、2、5和10 mmol·L-1组。用四氮唑盐（MTT）法测定CFs数目，流式细胞仪检测CFs细胞周期，液体闪烁计数仪测定CFs 3H-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，10-7 mol·L-1 ET-1能显著促CFs增值及3H]-Proline掺入率，降低CFs生成NO2-/NO3-的量（均P < 0.01），1～10 mmol·L-1 阿司匹林呈浓度依赖性的缓解上述变化（均P < 0.05）； ET-1能显著提高S期细胞百分率（P < 0.01），10 mmol·L-1 阿司匹林抑制ET-1诱导S期细胞百分率上升（P < 0.01）。结论 阿司匹林抑制ET-1诱导的CFs增殖及胶原合成可能和NO生成有关。

Aspirin inhibits the proliferation of rat cardiac fibroblasts induced by endothelin-1

Objective To investigate the effect of aspirin 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: control, ET-1, aspirin, ET-1 +aspirin 1 mmol/L, ET-1 +aspirin 2 mmol/L, ET-1 +aspirin 5 mmol/L and ET-1 + aspirinl 10 mmol/L. CFs were counted by MTr assay. Cell cycle distribution was determined with a flow cy-tometer (FCM). ~3H]-Proline incorporation was evaluated by scintillation counting. Nitric oxide (NO) was meas-ured by colorimetry. Results 10~(-7)mol/L ET-1 significantly increased the number of CFs and ~3H]-Pro incorporation and decreased NO_2~-/NO_3~--secretion compared with the control group (P <0.01).1 ～ 10 mmol/L Aspirin inhibited the effects of ET-1 on CFs in a concentration-dependent manner (P <0.05 vs ET-1). In the ET-1 group, the percent-age of cells in the S phase was higher than that of the control, which was inhibited by 10 mmol/L Aspirin (P <0.01 vs ET-1 and control). Conclusion Aspirin can restrain the proliferation and collagen synthesis of cardiac fibroblasts induced by endothelin-1, and this effect may be partially mediated by NO.