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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。
The purpose is to clarify the role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in myocardial reperfusion injury and to explore new ways to treat reperfusion injury using apocynin, a specific NADPH oxidase Inhibitors of myocardial reperfusion injury intervention, and its effect and mechanism were observed and analyzed. Methods The ischemia-reperfusion model in vivo was used to establish ischemia in the left anterior descending branch of rats for 30 min. The rats were then fasted for 3 h before reperfusion. Apocynin intervention group were given different doses of apocynin 10 min before reperfusion to observe the relationship between dose and cardioprotective effects. The indexes of cardiac function, infarct size, myocardial cell apoptosis, NADPH oxidase activity and free radical generation were also determined. Results After reperfusion, myocardial NADPH oxidase activity was significantly increased, and the generation of free radicals was also significantly increased. Apocynin can reduce the apoptosis and the free radical generation induced by myocardial reperfusion in a dose-dependent manner. Apocynin 10 mg / kg can improve cardiac function after reperfusion, reduce infarct size, reduce myocardial apoptosis and inhibit NADPH oxidation Enzyme activation, thereby reducing the generation of superoxide anion and peroxynitrite free radicals and their damage, but no significant effect on the formation of nitric oxide. Conclusions NADPH oxidase plays an important role in myocardial reperfusion injury. Apocynin can play a protective role in myocardial ischemia-reperfusion in rats. It can inhibit the activity of NADPH oxidase and decrease the activity of superoxide anion and peroxynitrite Related to the formation of salt free radicals.