标题：利用正交试验

      作者：筛选阿魏酸等四种药物干预在体大鼠MIRI凋亡最佳组合
    高宇勤 1，郝霁萍 1，贺少辉 1，赵国平 2
（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）

      卷次： 2015年26卷22期

      【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。

      【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

      【中图分类号】 R-332 【文献标识码】 A 【文章编号】 1003—6350（2015）22—3277—04


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.
GAO Yu-qin 1, HAO Ji-ping 1, HE Shao-hui 1, ZHAO Guo-ping 2. 1. Department of Cardiovascular Medicine, Ninth
Hospital of Xi'an, Xi'an 710054, Shaanxi, CHINA; 2. Department of Integrative Medicine, School of Medicine, Jinan
University, Guangzhou 510632, Guangdong, CHINA

【Abstract】 Objective To explore the effect of pretreatment with drug combinations of ferulic acid, and pae-
oniflorin, 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 estab-
lished by ligation of left descending coronary artery and reperfusion in SD rats. L16(44) orthogonal design, perfusion of
0.5% Evan's blue and incubation of 1% TTC were applied to observe myocardial infarction. Apoptotic index were de-
tected 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 ac-
id>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 (me-
dium dose, 200 mg/kg) is the optimum combination for lowering the myocardial apoptosis and reducing myocardial in-
farction area.

      【Key words】 Orthogonal design; Myocardial ischemia reperfusion injury (MIRI); Paeoniflorin; Glycyrrhizic
acid; Ferulic acid; Cinnamic acid
基金项目：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)