缓激肽介导的阿魏酸钠对离体大鼠心脏的药理性延迟保护作用

摘要

目的:研究阿魏酸钠(SF)对离体大鼠心脏急性缺氧/复氧(A/R)损伤的药理性预适应延迟保护作用及其与缓激肽的关系.方法:6组Wistar大鼠分别为对照(Cont)组、A/R组、缺氧预适应(APC)组、APC+HOE140组、SF组、SF+HOE140组.SF组、SF+HOE140组大鼠静脉注射SF 10 mg/kg;25 h后取大鼠心脏行Langendorff逆行灌流、制作A/R损伤模型.实验结束后分别检测LVP、±dp/dtmax等心功能指标、表面心电图、CF量以及其中LDH、CPK活性、心肌组织MDA含量与GSH-Px、SOD活性、心肌梗塞面积、心肌组织超微结构改变.结果:SF预处理能显著提高大鼠心脏LVP、±dp/dtmax、CF,降低LDH、CPK活性,SOD活性、GSHPx活性增加,MDA含量减少;大鼠心脏梗塞面积明显减少.HOE140能取消SF预处理的上述延迟保护作用.结论:SF预处理对心肌组织急性A/R损伤有明显的延迟保护作用,其机制与缓激肽系统活性增强有关.%Objective:To investigate the preconditioning delayed effects and mechanisms of sodium ferulate (SF) on isolated rat heart subjected to anoxia-reoxygenation (A/R) injury. Methods: 48 adult male Wistar rats were divided into six groups; control, A/R, anoxia preconditioning (APC), APC + H0E140, SF, SF + HOE140. The rats of SF and SF + HOE140 groups were intravenously administered SF 10 mg/kg, while the rats of other four groups were intravenously administered equal volume NS, respectively. After 25 hours, isolated rat hearts were perfused in Langendorff mode and subjected to A/R injury. The indexes of cardiac function such as ECG, left ventricular pressure (LVP) , ±dp/dt- max and CF volume were recorded. The activities of SOD, GSH-Px, LDH and CPK, the contents of MDA , the changes of ultrastructure in myocardium and the area of myocardial infarction were measured. Results: Pretreatment with SF decreased LDH activity, MDA contents, the area of myocardial infarction and arrhythmia, while increased the activities of SOD and GSH-Px, improved heart function and ultrastructure of myocardium. The delayed protective effects of SF were abolished by HOE140. Conclusion: SF can induce the delayed cardioprotection against acute A/R injury and the mechanisms may be related with the、enhancement of the activity of bradykinin system.