依达拉奉对大鼠缺血再灌注心肌的保护作用

Protective Effect of Edaravone on Myocardial Ischemia-Reperfusion Injury in Rats

目的探讨依达拉奉对心肌缺血再灌注的保护作用及机制。方法将50只成年SD大鼠按随机数字表法分为假手术组、再灌注组、低剂量组、中剂量组和高剂量组,每组10只。建立大鼠急性缺血再灌注模型,描记术中心电图变化。假手术组:开胸,分离左冠状动脉并穿线,不结扎,旷置225min;再灌注组:缺血45min,再灌注3h,灌注前1min将生理盐水按0.2mL·kg-1经右股静脉注入;低剂量组:再灌注前1min,将依达拉奉按3mg·kg-1经右股静脉注入;中剂量组:灌注前1min将依达拉奉按6mg·kg-1经右股静脉注入;高剂量组:灌注前1min将依达拉奉按9mg·kg-1经右股静脉注入。于再灌注末测定血清肌钙蛋白、心肌组织Ca2+、SOD、MDA及Na+-K+-ATPase、Ca2+-ATPase的含量或活性。结果再灌注组与低剂量组、中剂量组、高剂量组相比,再灌注后ST段回落程度较低、室性心律失常发作例数稍高,但4组间比较差异均无统计学意义(均P>0.05)。低剂量组、中剂量组和高剂量组的血清肌钙蛋白明显低于再灌注组(均P<0.05);中剂量组、高剂量组及再灌注组血清肌钙蛋白明显高于假手术组(P<0.05或P<0.01)。与假手术组比较,再灌注组心肌组织MDA活性、Ca2+含量明显增高,SOD活力及Na+-K+-ATP酶、Ca2+-ATP酶活性明显降低(均P<0.05);与再灌注组比较,低剂量组、中剂量组和高剂量组的MDA活力及Ca2+含量降低,SOD活力及Na+-K+-ATP酶、Ca2+-ATP酶活性明显增加(均P<0.05)。结论在再灌注前注射依达拉奉可减轻心肌缺血再灌注损伤。其作用机制是有效地清除氧自由基、提高机体抗氧化应激能力。

Objective To investigate the protective effect of edaravone on myocardial ischemiareperfusion injury and its potential mechanism of action. Methods Fifty SD rats were randomly divided into five groups,with 10 rats in each group. The rat model of acute myocardial ischemia and reperfusion was established and ECG changes were monitored during operation. In sham-operation group,left coronary artery was separated and threaded but unoccluded for 225 minutes. In reperfusion group, rats were subjected to 45 minutes of ischemia and then injected with normal saline （0.2 mL ·kg-1） through the right femoral vein 1 minute before 3 hours of reperfusion. In addition,low-dose group, medium-dose group and high-dose group were injected with edaravone at doses of 3,6 and 9 mg·kg-1 through the right femoral vein / minute before reperfusion,respectively. The levels of serum troponin and the contents or activities of myocardial calcium ions,superoxide dismutase （SOD） ,malonaldehyde （MDA） ,Na＋-K＋ ATPase and Ca2＋-ATPase were detected at the end of reperfusion. Results Compared with edaravone groups, the reduction in ST segment after reperfusion decreased and the incidence of ventricular arrhythmias increased in reperfusion group. But the differences were not significant among reperfusion group, low-dose group,medium-dose group and high-dose group （P〈0.05）. Compared with reperfusion group,se- rum levels of troponin and myocardial activities of SOD,Na＋-K＋-ATPase and Ca2＋-ATPase sig nificantly increased but myocardial contents of MDA and calcium ions significantly decreased in low-dose group, medium-dose group and high-dose group （all P〈0.05）. Compared with sham-operation group, serum levels of troponin obviously increased in medium-dose group, high-dose group and reperfusion group, and myocardial contents of MDA and calcium ions obviously in- creased and activities of SOD,Na＋ -K＋ -ATPase and Ca2＋ -ATPas obviously decreased in low-dose group,medium-dose group and high-dose group （P〈0.05 or P〈0.01）. Conclusion Edaravone injected before the onset of coronary reperfusion can attenuate myocardial ischemia-reperfusion injury. The mechanism may be associated with the ability to scavenge oxygen free radicals and strengthen the resistance to oxidative stress.