氯沙坦对心力衰竭大鼠心肌细胞缝隙连接的作用机制研究

目的观察氯沙坦对心力衰竭(心衰)大鼠心功能的影响并探讨其对心肌细胞缝隙连接的作用机制。方法 SD大鼠60只随机分为假手术组、模型组、氯沙坦高、中、低剂量组,灌胃给药7 d后,采用冠脉结扎复制大鼠心衰模型。测定心功能:左心室压峰值(LVP)、左心室舒张末期压(LVEDP)、左心室内压最大上升速率(+LVdp/dtmax)、左心室内压最大下降速率(-LVdp/dtmax)。采用Western Blot方法测定心肌缝隙连接蛋白43(Cx43)和Cx45的表达。结果氯沙坦能显著改善心衰大鼠心功能,与模型组比较,氯沙坦低、中剂组LVP明显上升(P<0.01),LVEDP明显下降(P<0.05或<0.01),高剂组LVP、+LVdp/dtmax明显上升,LVEDP明显下降(P<0.01);显著提高Cx43表达,降低Cx45表达(P<0.05或<0.01)。结论氯沙坦对心室的间隙连接通道有保护作用,可以提高心室传导速度,从而降低心律失常的发生。

Effects of losartan on myocardial cell gap junctions in rats with heart failure

Objective To investigate the effect of losartan on cardiac function and possible action mechanism of myocardial cell gap junctions in rats with heart failure.Methods The 60 SD rats were randomly divided into five groups:sham-operation group,model group,losartan high,middle,low dose groups.The rats in all the groups were irrigated for 7 days.The experimental heart failure models were established by coronary artery ligation.The cardiac function was determined including LVP,LVEDP,+LVdp/dtmax,-LVdp/dtmax.Western blot was used to detect the expression levels of myocardial cell gap junctions protein Cx43 and Cx45.Results Losartan could obviously improve cardiac function.As compared with model group,losartan middle-dose and low-dose groups could significantly increase LVP(P<0.01),decrease LVEDP(P<0.05 or P<0.01);losartan high-dose group could increase LVP,+LVdp/dtmax,decrease LVEDP(P<0.01);losartan could obviously increase the expression of Cx43,decrease the expression of Cx45(P<0.05 or P<0.01).Conclusion Losartan can improve cardiac function of rats with heart failure and the action mechanism may be related with the protection of myocardial cell gap junctions channels.