不同水平干预对AngII作用心肌细胞活力的影响

目的 :通过使用血管紧张素II(AngII)两种亚型受体AT1 R、AT2 R拮抗剂 (Valsartan和CGP4 2 112A)及丝裂素活化蛋白激酶 (MAPK)特异阻断剂 ,观察对心肌细胞活力的影响 ,探讨从受体和MAPK信号不同水平的阻断是否能有效干预心肌细胞能量代谢 ,为寻找新的心衰预防与治疗药物提供实验依据。方法 :应用MTT比色法测定AngII对培养心肌细胞活力的影响和AngII受体拮抗剂及MAPK抑制剂的干预作用。 结果 :AngII刺激心肌细胞在10 8～ 10 5mol/L浓度范围 ,一定时间内呈浓度依赖性增加心肌细胞活力变化 ;使用Valsartan、PD980 5 9可有效抑制AngII引起的心肌细胞活力改变 ;CGP4 2 112A干预后对AngII作用无明显影响。 结论 :AngII的作用主要通过AT1 R介导 ;与细胞增殖、分化密切相关的ERK信号介入了心肌细胞能量代谢的过程 ,这对了解AngII在心功能不全代偿和心力衰竭发生中的作用及临床上探讨细胞信号系统不同层面对心衰进行干预具有重要参考价值。

Different interventions inhibit the effects of angiotensin II on the cardiomyocyte viability

Objective:We investigated the inhibitory effects of AngII receptor antagonists Valsartan, CGP42112A and MAPK blocker PD098059 on the AngII-induced cardiac myocyte viability in order to observe whether different interferences can effectively influence the cellular energy metabolism and provide the new experimental evidence for the application of those agents in pharmacological therapy of congestive heart failure. Methods:Based on that the mitochondria of viable cells can act on MTT to produce formazan of the purple, we investigate the effect of AngII on the cultured myocyte viability and the intervention of Valsartan, CGP42112A and PD098059 by means of colorimetric method. Results:Our results showed that AngII caused the gradual increase of formazan optical density(OD) within definite concentration and time,and then decreased, even lower than the normal after about 24 hours. CGP42112A had no distinct effect of AngII on the cardiac myocyte viability, but Valsartan and PD098059 had the inhibiting effect, respectively. Conclusion:AngII-induced myocyte viability is mainly mediated by AT 1-Rand ERK is concerned with cellular energy metabolism.That has important meanings for the application of different interferences among the cellular signal transduction in pharmacological therapy of congestive heart failure in the future.