香草乙酮对大鼠心肌再灌注损伤的保护作用  

Apocynin and its heart protective effect in rats from reperfusion injury

作　　者：焦向英[1] 赵晓琴[1] 张燕[1] 赵荣瑞[1] 

机构地区：[1]山西医科大学生理学系山西医科大学细胞生理学省部共建重点实验室,太原030001

出　　处：《中国预防医学杂志》2010年第3期220-224,共5页Chinese Preventive Medicine

基　　金：国家自然基金项目(30800399);山西省自然基金项目(2009011056-1);山西省回国留学人员科研资助项目(2009-46);山西医科大学创新基金资助

摘　　要：目的为明确烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶在心肌再灌注损伤中的作用,并探索治疗再灌注损伤的新途径,使用香草乙酮(apocynin)这一特异的NADPH氧化酶抑制剂对心肌再灌注损伤进行干预,并对其效果和机制进行了观察分析。方法使用在体大鼠心脏缺血再灌注模型,给予30 min左前降支结扎造成缺血,随后松扎进行3 h再灌注。Apocynin干预组于再灌注前10 min给予不同剂量的apocynin,观察其剂量与心脏保护效应关系,并测定心功能、梗死面积、心肌细胞凋亡、NADPH氧化酶活性和自由基生成等指标。结果再灌注后心肌NADPH氧化酶活性明显升高,自由基生成也显著增加。给予apocynin可剂量依赖性地减轻心肌再灌注引起的细胞凋亡和自由基生成,apocynin 10 mg/kg剂量可以改善再灌注后的心脏功能,缩小梗死面积,减少心肌凋亡的发生,抑制NADPH氧化酶的活化,从而减少超氧阴离子和过氧化亚硝酸盐自由基的生成及其损伤,但对一氧化氮的生成无明显影响。结论NADPH氧化酶在心肌再灌注损伤中发挥重要作用,apocynin可以对再灌注大鼠心肌发挥保护作用,这种保护与其抑制NADPH氧化酶的活性,减少其介导的超氧阴离子和过氧化亚硝酸盐自由基生成有关。Objective To study the effect of apocynin,a NADPH oxidase inhibitor,on rat heart protection from reperfusion injury.Methods An in vivo rat heart ischemia reperfusion model was used,and the left anterior descending coronary artery was ligated for 30 min to develop ischemia and followed by 3 hours reperfusion.Apocynin of different doses were administrated 10 minutes before reperfusion to evaluate dose-dependent effect.Mice of the groups treated with the different doses of apocynin were assayed for cardiac function,infarct size,cardiomyocyte apoptosis,NADPH oxidase activity and reactive oxygen species production.Results After reperfusion,the expression and activity of heart NADPH oxidase increased significantly.Free radical production also increased accordingly.Apocynin decreased reperfusion induced cardiomyocyte apoptosis and free radical production.A dose of 10 mg/kg apocynin was able to provide protective effects.Apocynin improved cardiac function,reduced infract size and apoptosis,inhibited NADPH oxidase activity thus decreased superoxide anion and peroxynitrite production,while no effect on nitric oxide generation was confirmed.Conclusion NADPH oxidase played an important role in heart reperfusion,which could be inhibited by apocynin.Apocynin reduced NADPH oxidase dependent superoxide anion and peroxynitrite production and their injuries to provide heart protection.

关 键 词：再灌注损伤 香草乙酮 大鼠 NADPH氧化酶 过氧化亚硝酸盐 

分 类 号：R541[医药卫生—心血管疾病]