奥帕曲拉对内皮素-1诱导的大鼠心肌细胞肥大的影响

 摘要： 目的 探讨奥帕曲拉（OMA）对内皮素-1（ET-1）诱导的大鼠心肌细胞肥大的作用及其机制。方法 经差速贴壁法获得乳鼠心肌细胞，随机分为对照组、ET-1组、OMA 组、ET-1＋OMA组、ET-1＋OMA＋L-NAME组和ET-1＋OMA＋HS-142-1（GC受体阻断剂）组。用分光光度法测定NOS活性, 放射免疫法测定细胞内cGMP水平；液体闪烁计数仪测定3H-亮氨酸（3H]-leu）掺入率及蛋白激酶C (PKC)活性；用HJ2000图像分析系统测定细胞表面积。结果10-6mol/L ET-1能显著增加心肌细胞表面积、PKC活性及3H]-leu 掺入率, 降低NOS活性及 cGMP含量 (均P < 0.01); 10-7 mol/L OMA能显著抑制ET-1的上述作用（均P < 0.01），L-NAME、HS-142-1可部分阻断OMA的作用。结论OMA能抑制ET-1诱导的心肌细胞肥大效应，该作用部分通过NO/cGMP、PKC调控。

The effect of omapatrilat on endothelin-1-induced cardiomyocyte hypertrophy in neonatal rats

Abstract：Aim To investigate omapatrilat on endothelin-1 (ET-1)-induced cardiomyocyte hypertrophy in neonatal rats. Methods Isolated and cultured cardiomyocyte of neonatal Sprague-Danley (SD) rats were randomly divided into 6 groups: control, ET-1, OMA, ET-1＋OMA,ET-1＋OMA＋L-NAME and ET-1＋OMA＋HS-142-1. Nitric Oxide synthetase (NOS) activity was measured by Spectrophotometry. Intracellular cyclic GMP (cGMP) were measured by radioimmunoassay. 3H]-leu incorporation and PKC activity were evaluated by scintillation. Results Compared with the control group, 10-6mol/L ET-1 significantly increased the surface area, the activity of PKC and 3H]-leu incorporation of cardiomyocyte, decreased the activity of NOS and cGMP content (P < 0.01 for all); 10-7 mol/L OMA inhibited the above effects of ET-1 on cardiomyocyte (P < 0.01 v.s ET-1). L-NAME, HS-142-1 partially blocked the inhibitory effects of OMA ( P < 0.05). Conclusion The NO/cGMP and PKC may partially mediate the antiproliferation action of OMA in ET-1-induced cardiomyocyte hypertrophy.