卡立泊来德与维拉帕米对大鼠缺血再灌注心肌保护作用的比较研究

目的比较Na+/H+交换抑制剂卡立泊来德(cariporide)和钙离子拮抗剂维拉帕米(verapamil)这两类药物对于心肌保护作用的差别,从而给寻找更有效的心肌保护药物提供参考。方法建立大鼠在体心肌冠状动脉左前降支(LAD)缺血再灌注损伤模型,实验大鼠随机分为5组,每组6只,即伪手术组(LAD下只穿线不结扎)、对照组(缺血再灌注组,不给药)、卡立泊来德治疗组、维拉帕米治疗组、卡立泊来德与维拉帕米合用组。结扎LAD30min后松解结扎线,开始再灌注,再灌注60min后结束实验。于再灌注前分别应用卡立泊来德和维拉帕米,从心电图ST段变化、心肌损伤标志物肌钙蛋白I及肌红蛋白定量检测和心肌超微结构改变等方面探讨比较这两类药物对于心肌保护作用的差别。结果肌红蛋白值各组间差异无统计学意义(P>0.05),肌钙蛋白I值示组间差异有统计学意义(P<0.05)。卡立泊来德组、维拉帕米组及卡立泊来德与维拉帕米合用组肌钙蛋白I值与对照组比较差异有统计学意义(P<0.05);卡立泊来德组、维拉帕米组及卡立泊来德与维拉帕米合用组之间肌钙蛋白I值两两比较差异无统计学意义(P>0.05)。心电图ST值变化趋势结果示,卡立泊来德组与对照组ST值变化趋势比较差异有统计学意义(P<0.05),维拉帕米组与对照组ST值变化趋势比较差异无统计学意义(P>0.05),卡立泊来德组与维拉帕米组ST值变化趋势比较差异无统计学意义(P>0.05)。心肌细胞超微结构电镜观察结果示卡立泊来德组、维拉帕米组及卡立泊来德与维拉帕米合用组心肌细胞结构损伤较对照组轻,但三组间差异不明显。结论卡立泊来德与维拉帕米有一定的心肌保护作用,单一应用卡立泊来德的心肌保护效果较单一应用维拉帕米无明显优势,两者合用的效果并不优于单用其一者。

Comparison of protective effects of cariporide and verapamil on myocardial ischemia reperfusion injury in rats

Objective To compare the protective effects of cariporide and verapamil on myocardial ischemia reperfusion injury. Methods Thirty Wistar rats(weights 250～290 g) were randomly divided into five groups(n=6 each group):Group Ⅰ(normal) group; Group Ⅱ(ischemia-reperfusion injury group),subjected to 30 min occlusion and 60 min reperfusion; Group Ⅲ(apply Cariporide group); Group Ⅳ(apply verapamil group); Group Ⅴ(apply cariporide & verapamil group). Rats ischemia reperfusion model was established by ligation of left anterior descending coronary. Group Ⅲ、Ⅳ、Ⅴ,also subjected to 30 min occlusion and 60 min reperfusion,cariporide and verapamil and cariporide & verapamil were given iv after 30 min myocardium ischemia respectively. The changes of voltage of ST of ECG in Ⅱ lead and amount of cardiac troponin I(cTnI) and myoglobin(Mb) in plasma on acute ischemia and reperfusion were examined. Myocardial ultrastructures were examined under transmission electron microscope. Results The amount of Mb in plasma had no significant difference among each groups (P>0.05). The amount of cTnI in plasma in group Ⅲ、 Ⅳ、Ⅴ were lower than that of ischemia-reperfusion injury group(P<0.05),but had no significant difference among the group Ⅲ、Ⅳ、Ⅴ(P>0.05). The changes of voltage of ST in Ⅱ-lead electrocardiogram were significant difference between group Ⅱ and group Ⅲ(P<0.05),but had no significant difference between group Ⅱ and group Ⅳ(P>0.05),and between group Ⅲ and group Ⅳ(P>0.05). The myocardial ultrastructural changes were significant in group Ⅱ,there were significant edema in myocardium and in mitochondria,severe damage in mitochondria; but there were not so severe in group Ⅲ、Ⅳ、Ⅴ. Conclusion Both cariporide and verapamil show protective effects on myocardial ischemia reperfusion but the protective effect of cariporide was no better than that of verapamil. Cariporide&Verapamil combined apply had no better protective effect than that of single applying one of the two.