内皮素-1对大鼠离体心脏缺血再灌注损伤的保护作用

Protective effect of endothelin-1 for ischemia/reperfusion injury in the isolated rat heart

目的观察内皮素-1（ET-1）对大鼠离体心脏缺血再灌注损伤的影响以及不同浓度ET-1的不同效应。方法健康雄性SD大鼠30只,体重250-300 g,建立Langendorff离体心脏灌注模型。随机分为5组：对照组、ET-1组（0.1、1、10 nmol/L）和BQ-123组（2μmol/L）,每组6只。所有离体心脏均平衡20 min,全心缺血30 min,再灌注60 min。观察各组在缺血再灌注损伤后各时间点的左室发展压（LVDP）、左室舒张末压（LVEDP）、冠脉流量（CF）以及冠脉流出液中乳酸脱氢酶（LDH）和肌酸激酶（CK）的变化。结果再灌注后,与对照组相比,ET-1组的LVDP明显升高,LVEDP显著降低,CF也稍有升高。ET-1组再灌注5 min后的LDH、CK较对照组明显下降,而且,低剂量ET-1组（0.1、1 nmol/L）效果更显著。但是,ET-1组的效果被BQ-123所抑制。结论 ET-1对离体心脏缺血再灌注损伤具有一定的保护作用,且低剂量时效果更显著,这种保护作用可能是由ETA受体所介导。

Objective The aim of present study was to investigate the influence of endothelin-1（ET-1） to the ischemia and reperfusion injury in the isolated rat heart and different responses to different doses of ET-1. Methods Thirty healthy male SD rats（250 - 300 g） were randomly divided into five groups. The control group, ET-1 groups which is divided into three groups（0.1 nmol / L, 1 nmol / L, 10 nmol / L） and BQ-123 group（2 μmol / L）. All the isolated rat hearts were connected to Langendorff apparatus. After 20 min stabilization, the hearts were subjected to global ischemia 30 min, followed by 60 min of reperfusion.Hemodynamic parameters（LVDP, LVEDP, CF） were registered throughout the experiments. LDH and CK in the coronary effluent were examined. Results Lower doses（0.1 nmol / L, 1 nmol / L） of ET-1 significantly improved left ventricular function after reperfusion, such as indices of LVDP, CF were improved, and LVEDP was reduced. In addition, ET-1 reduced the level of LDH and CK. But these effects of ET-1 were markedly attenuated by BQ-123. Conclusion The data suggests that ET-1evokes a cardioprotective effect against ischemia / reperfusion injury. And the lower dose has more potent effect. This ET-1preferentially binds to ETA receptors to exert its related beneficial actions.