目的:研究依达拉奉(Edaravone)对大鼠离体心肌缺血再灌注损伤的保护作用。方法:将54只SD大鼠随机分为3组,包括对照组(control group),缺血再灌注组(I/R group),依达拉奉组(Ed group)。灌注液为K-H液,37℃下建立心肌缺血再灌注模型,预灌注15min,缺血30min,再灌注40min,分别测量①复灌20和40min时心功能指标:心率(HR)、左室收缩压(LVDP)、左室舒张末压(LVEDP)、心室内压最大变化速率(±dp/dtmax),②复灌20和40min时肌酸激酶(CK)和乳酸脱氢酶(LDH)活性,③复灌40min时超氧化物歧化酶(SOD)活性和丙二醛(MDA)浓度,④复灌40min时心肌梗死面积,⑤复灌40min时心肌组织中JNK的磷酸化水平。结果:①依达拉奉组的±dp/dtmax明显回升(P〈0.05),同时LVEDP、LVDP等指标也有明显改善(P〈0.05);②再灌注40min时,与缺血再灌注组比,依达拉奉明显降低LDH和CK;③依达拉奉能显著降低MDA浓度,同时提高SOD水平(P〈0.05);④依达拉奉组心肌梗死面积小于缺血再灌注组(P〈0.05);⑤依达拉奉降低缺血心肌组织中磷酸化JNK的水平(P〈0.05)。结论:依达拉奉可以改善缺血心肌的血流动力学,增加心肌收缩力,减少心肌梗死面积;能发挥清除氧自由基,扭转氧化与抗氧化平衡系统失调的作用;其对离体心肌缺血再灌注的保护作用可能与JNK途径密切相关。
Objective:To investigate the protective effect of edaravone on myocardial ischemic and reperfusion injury.Methods:Fifty-four SD rats were randomly divided into three groups, control group, ischemia reperfusion injury group, and edaravone group.The animals were sacrificed and the hearts were immediately removed apparatus and perfused with K-H solution satduated at 37℃.Then the hearts were subjected to 30 min ischemia followed 40 min reperfusion.The HR, LVDP, LVEDP and ±dp/dtmax were recorded before ischemia and at 20 and 40 min of reperfusion.The coronary effulent were collected before ischemia and at 20 and 40 min of reperfusion to measure the CK and LDH activity.At the end of the reperfusion, the SOD activity,MDA content, the infarct size and the JNK activity were determined.Results:The LVEDP, LVDP and ±dp/dtmax were better in Edaravone group than that in ischemia and reperfusion group.The MDA content, the infarct size, the CK and LDH activity were lower in Edaravone group than that in ischemia and reperfusion group.And the JNK activity was also lower in Edaravone group.The SOD activity was higher in Edaravone group than that in ischemia and reperfusion group.Conclusion:Edaravone has protective effect on isolated myocardial ischemia and reperfusion injury, and the JNK signaling pathway may play an important role in the mechanism.