利用正交试验筛选阿魏酸等四种药物干预在体大鼠MIRI凋亡最佳组合  

Screening of optimum drug combination of ferulic acid, paeoniflorin, glycyrrhizic acid and cinnamic acid for anti-cardiomyocyte apoptosis in the myocardial ischemia reperfusion injury of rats by orthogonal design in vivo

作　　者：高宇勤 郝霁萍 贺少辉 赵国平[2] 

机构地区：[1]西安市第九医院心血管内科,陕西西安710054 [2]暨南大学医学院中西医结合科,广东广州510632

出　　处：《海南医学》2015年第22期3277-3280,共4页Hainan Medical Journal

基　　金：国家自然科学基金(编号:81173189);西安市卫生局科技项目及西安市科技项目(编号:SF1416)

摘　　要：目的利用正交实验方法探究阿魏酸、芍药苷、甘草酸及肉桂酸四种药物组合预处理对大鼠在体心肌缺血再灌注损伤(MIRI)的心肌细胞凋亡的干预作用,并寻找最佳药物组合。方法本实验采用了结扎SD大鼠心脏冠状动脉前降支(LA)的方法建立在体大鼠心肌缺血再灌注损伤模型;采用L16(44)正交实验设计和0.5%Evan's蓝灌注心肌及1%TTC磷酸缓冲液孵育心肌观察心肌坏死;利用TUNEL法检测心肌细胞凋亡。结果比较各因素的极差发现阿魏酸、甘草酸、芍药苷、肉桂酸对大鼠MIRI模型心肌梗死面积影响的顺序是:芍药苷>甘草酸>阿魏酸>肉桂酸;阿魏酸、甘草酸、芍药苷、肉桂酸对大鼠MIRI模型的心肌细胞凋亡指数影响的顺序是:芍药苷>甘草酸>肉桂酸>阿魏酸;阿魏酸、甘草酸、芍药苷、肉桂酸四药混合干预大鼠MIRI心肌细胞凋亡指数最佳选择方案是:芍药苷(高剂量,100 mg/kg)、甘草酸(高剂量,100 mg/kg)、阿魏酸(中剂量,300 mg/kg)、肉桂酸(中剂量,200 mg/kg)。结论芍药苷(高剂量,100 mg/kg)、甘草酸(高剂量,100 mg/kg)、阿魏酸(中剂量,300 mg/kg)、肉桂酸(中剂量,200 mg/kg)组合是降低心肌细胞凋亡、减少心肌梗死面积的最佳组合。Objective To explore the effect of pretreatment with drug combinations of ferulic acid, and paeoniflorin, glycyrrhizic acid and cinnamic acid on cardiomyocyte apoptosis in myocardial ischemia reperfusion injury in rats, and to find the best drug combination. Methods Myocardial ischemia reperfusion injury models were established by ligation of left descending coronary artery and reperfusion in SD rats. L16（4^4） orthogonal design, perfusion of0.5% Evan＇s blue and incubation of 1% TTC were applied to observe myocardial infarction. Apoptotic index were detected by TUNEL. Results The four drugs＇ effect on reducing infarct size of myocardium after ischemia/reperfusion from high to low was peoniflorin〉glycyrrhizic acid〉ferulic acid〉cinnamic acid, and the effect on reducing apoptotic index of myocardium after ischemia/reperfusion from high to low was peoniflorin〉glycyrrhizic acid〉cinnamic acid〉ferulic acid. The optimum drug combination was peoniflorin（100 mg/kg）, glycyrrhizic acid（100 mg/kg）, cinnamic acid（200 mg/kg） and ferulic acid（300 mg/kg）. Conclusion The drug combination of paeoniflorin（high dose,100 mg/kg）, glycyrrhizic acid（high dose, 100 mg/kg）, ferulic acid（medium dose, 300 mg/kg） and cinnamic acid（medium dose, 200 mg/kg） is the optimum combination for lowering the myocardial apoptosis and reducing myocardial infarction area.

关 键 词：正交试验 心肌缺血再灌注损伤 芍药苷 甘草酸 阿魏酸 肉桂酸 

分 类 号：R-332[医药卫生]