川芎嗪对大鼠心肌细胞氧糖剥夺/复氧损伤的保护作用及机制研究  

The protective effect of tetramethylpyrazine on rat myocytes with transient oxygen-glucose deprivation followed by reoxygenation injury and mechanism study

作　　者：张瑞 沈承武[1] 闫根全[1] ZHANG Rui;SHEN Cheng-wu;YAN Gen-quan(Department of Pharmacy, Shandong Provincial Hospital affiliated to Shandong University, Ji' nan 250021, China)

机构地区：[1]山东大学附属省立医院药学部,山东济南250021

出　　处：《中国生化药物杂志》2017年第9期10-13,共4页Chinese Journal of Biochemical Pharmaceutics

摘　　要：目的研究川芎嗪（tetramethylpyrazine）对心肌缺血再灌注损伤的保护作用，并探究其作用机制。方法原代培养大鼠心肌细胞，建立心肌细胞氧糖剥夺/复氧损伤模型：MTT方法测定细胞存活率；紫外分光光度法测定细胞培养基上清液中LDH、CK、NO水平和心肌细胞内SOD、MDA水平；Westernblot方法检测细胞内eNOS和iNOS蛋白的表达水平。结果川芎嗪能够显著改善大鼠心肌细胞氧糖剥夺/复氧损伤心肌细胞搏动频率，降低LDH、CK及NO释放水平，抑制MDA表达，提高SOD活性，下调细胞内iNOS蛋白表达水平，上调eNOS蛋白表达水平。结论川芎嗪能够显著抑制氧化应激反应，从而增强心肌细胞对于过量氧自由基损伤的耐受能力，保持心肌细胞膜的完整性和保护心肌组织的正常生理功能。川芎嗪能够平衡eNOS/iNOS两种蛋白的表达，维持体内NO正常浓度，防止过量NO所造成的心肌组织损伤。Objective This study explored the protective effect of tetramethylpyrazine on myocardial ischemia/reperfusion injury viainhibiting oxidative stress.Methods Primary cultured neonatal myocytes were applied to explore the anti-ischemia/reperfusion injury propertyin vitro.The survival viability of myocytes was determined by MTT;enzyme activities such as lactate dehydrogenase,creatine kinase,superoxidedismutase,malondialdehyde,and nitric oxide were analyzed with assay kits;inducible nitricoxide synthase and endothelial nitric oxide synthaseexpressions were determined by Westernblot.Results Tetramethylpyrazine significantly improved the beating frequencies of myocytes after oxygenglucosedeprivation/reoxygenation procedure,decreased lactate dehydrogenase,creatine kinase,and malondialdehyde levels and enhanced superoxidedismutase activity.Tetramethylpyrazine also inhibited excessive production of nitric oxide through downregulating inducible nitric oxide synthaseas well as upregulating endothelial nitric oxide synthase during ischemia/reperfusion injury.Conclusion Tetramethylpyrazine could significantlyimprove the oxidative-stress tolerance of myocytes to keep cell membrane integrity and protect the myocardial tissue of normal physiological functionvia an antioxidant effect and by restoring the balance between inducible nitric oxide synthase and endothelial nitric oxide synthase,while inhibitingthe generation of cytotoxic concentrations of NO.

关 键 词：川芎嗪 心肌细胞 氧化应激 氧糖剥夺/复氧 保护作用及机制 

分 类 号：R453.9[医药卫生—治疗学]