氧化苦参碱对大鼠冠脉结扎诱发急性心肌梗死的保护作用及机制

目的:研究氧化苦参碱( oxymatrine,OMT)对大鼠冠脉结扎诱发急性实验性心肌梗死的作用及可能作用机制.方法:SD大鼠按体重随机分为4组:假手术组、模型组、OMT 50,25 mg· kg -1组,各组ig给药,连续5d.末次给药后1h结扎冠状动脉左前降支(LAD)复制大鼠急性实验性心肌梗死模型,6h后,收集分析标本.HE染色观察大鼠心肌组织病理形态学变化,生化分析法检测血清中过氧化氢酶(CAT)、超氧化物岐化酶(SOD)、谷胱甘肽过氧化物酶(GSH -Px)的活力,总抗氧化能力(T-AOC)及丙二醛(MDA)含量,ELISA法分析血清中白介素-1β(IL-1β)、白介素-6(IL-6)、和肿瘤坏死因子-α(TNF-α)的水平.结果:OMT 50 mg·kg-1组能明显改善急性心肌梗死所致心肌组织间质水肿、炎细胞浸润等病理组织学改变；提高心肌梗死大鼠血清中SOD,CAT,GHS-Px活性,降低大鼠血清中MDA含量(与模型组比较,P＜0.05或P＜0.01)；降低心肌梗死大鼠血清中IL-1β,IL-6,TNF-α的水平(P＜0.05或P＜0.01)；对血清中T-AOC未见明显影响.结论:OMT对大鼠冠状动脉结扎诱发实验性急性心肌梗死具有一定的保护作用,其作用机制可能与抑制免疫炎症因子分泌和改善氧化应激状态有关.

Protective Mechanism of Oxymatrine on Acute Experimental Myocardial Infarction in Rats Induced by Ligatting Left Anterior Descending Branch of Coronary Artery

Objective:To investigate the protective effects and mechanism of oxymatrine(OMT) on experimental acute myocardial infarction(AMI) in rats induced by ligatting left anterior descending branch of coronary artery.Method:The SD rats were allotted into 4 groups according to the body weight as following:sham operation,model group,the OMT 50 mg·kg-1and 25 mg·kg-1 groups,the rats were orally administered for 5 days.The rat AMI model was reproduced by ligation of left anterior descending branch of coronary artery after 1 hour of the last treatment,the ligation of the artery did not be performed in sham operation group.The sample was collected after ligation of left anterior descending branch of coronary artery for 6 hours.The pathological changes of cardiac tissue were checked by HE staining.The indexes of oxidative stress were detected by biochemical assay kits,including the total antioxidant capacity(T-AOC),activities of superoxide dismutase(SOD),catalase(CAT),glutathione peroxidase(GSH-Px),and malondialdedyde(MDA) content.And the contents of the interleutin-1β(IL-1β),interleutin-6(IL-6),and tumor necrosis factor-α(TNF-α) in serum were measured by Elisa kits.Result:The histological examination indicated there was a myocardial lesion in model group including edema of myocardial interstitial and inflammatory cell infiltration,etc,after ligation of left anterior descending branch of coronary artery,OMT 50 mg·kg-1 could ameliorate the histopathological changes.The activities of antioxidant enzymes in serum were significantly decreased such as SOD,CAT,and GSH-Px,as well as MDA contents in serum were increased,and the contents of IL-1β,IL-6,and TNF-α in serum were increased in model group(compared with sham group,there were significant difference,P<0.01 or P<0.05).50 mg·kg-1 OMT could obviously ameliorate oxidative stress and inflammatory cytokines in serum(compared with model group,P<0.01 or P<0.05).Conclusion:OMT can protect the cardiac injury in rats induced by ligating left anterior descending branch of coronary artery,the mechanism maybe involve in inhibiting secretion of inflammatory cytokines and ameliorating oxidative stress.