目的研究氧化苦参碱对心肌缺血的保护作用,并进一步探讨其可能的作用靶点。方法采用结扎大鼠左冠状动脉前降支制备急性心肌缺血模型,观察氧化苦参碱对心肌缺血的保护作用;应用TUNEL法检测氧化苦参碱对心肌缺血大鼠心肌细胞凋亡指数的影响;应用半定量逆转录聚合酶链式反应(RT-PCR)研究氧化苦参碱对急性心肌缺血大鼠心肌L型Ca²⁺通道蛋白mRNA表达的作用。结果氧化苦参碱大、中、小剂量(20、10、5mg/kg)组均可缩小心肌梗死面积;氧化苦参碱大、中剂量能明显提高血清SOD活力、降低MDA水平;TUNEL法证实氧化苦参碱可降低心肌细胞凋亡指数;RT-PCR检测结果表明,急性心肌缺血大鼠心肌L型Ca²⁺通道蛋白α_1CmR-NA表达水平明显高于假手术组(P<0.01),经氧化苦参碱治疗后,心肌L型Ca²⁺通道蛋白α_1CmRNA表达降低(P<0.05)。结论氧化苦参碱对大鼠急性心肌缺血具有保护作用,其机制可能与抑制脂质过氧化,降低大鼠心肌L型Ca²⁺通道蛋白α1CmRNA表达,从而抑制心肌细胞凋亡有关。

Objective To investigate the protective effects of oxymatrine on myocardial ischemia and further explore their underlying targets.Methods The effects of oxymatrine on myocardial ischemia were observed by a model of acute myocardial infarction due to permanent ligation of left anterior descending coronary artery in rats.The apoptotic index of cardiomyocyte was detected by terminal deoxynucleotid transferase directed d-UTP nick and end labeling(TUNEL)assay.RT-PCR technique was utilized to study the action of oxymatrine on expression of L-type calcium channel protein α^1C mRNA in the cardiomyocytes of rats.Results Oxymatrine could decrease infarct area of myocardium at the dose of 5,10,and 20 mg/kg.Oxymatrine could also increase SOD activity,reduce MDA content in serum,and attenuate myocyte apoptosis.The results of RT-PCR showed the expression of L-type calcium channel protein α^1C mRNA in model rats was markedly increased(compared with that in Sham-operation rats)(P<0.01),and after treatment with oxymatrine,the expression of L-type calcium channel protein α^1CmRNA was lower than that in model rats(P<0.05).Conclusion Oxymatrine possesses protective action on myocardial infarction of rats.The possible mechanisms of anti-ischemia are attributed to decreasing the expression of L-type calcium channel protein α^1C mRNA in ventricular myocytes of rats and further inhibiting cardiomyocyte apoptosis.

国家自然科学基金重点项目(30430780)；哈尔滨医科大学研究生创新基金