芹菜素对大鼠缺血/再灌注心肌细胞凋亡及相关蛋白Bcl-2、Bax、Caspase-3表达的影响  

Effect of apigenin on the cardiomyocyte apoptosis in rats with ischemia and reperfusion and the expression of Bcl-2,Bax,Caspase-3

作　　者：史婷婷[1] 白建平[2] 梁月琴[1] 张慧芝[2] 于肯明[2] 李超鹏[3] 

机构地区：[1]山西医科大学基础医学院药理学教研室,山西太原030001 [2]山西大同大学药理学教研室,山西大同037009 [3]山西医科大学第一医院泌尿科,山西太原030001

出　　处：《中国药理学通报》2011年第5期666-671,共6页Chinese Pharmacological Bulletin

摘　　要：目的探讨黄酮类化合物芹菜素对大鼠实验性心肌缺血/再灌注(ischemia/reperfusion,I/R)时心肌细胞凋亡与Bcl-2、Bax、Caspase-3蛋白表达的影响,并分析心肌组织病理学损伤程度。方法采用结扎左冠状动脉前降支,心肌缺血45 min,再灌注2 h制作缺血/再灌注模型。将大鼠随机分为8组,即正常组(normal group,Normal)、假手术组(sham oper-ation group,Sham)、生理盐水缺血/再灌注组(saline ischemi-a-reperfusion group,NS)、溶剂对照组(solvent control group,Sol)、美托洛尔对照组(metoprolol control group,Meto)、芹菜素低、中、高剂量(1、2、4 mg.kg-1)用药组(apigenin low,medium and high dose treatment group,Api1,Api2,Api4)。再灌注2 h后迅速取出心脏,TUNEL法原位标记凋亡的心肌细胞;免疫组化法测Bcl-2、Bax和Caspase-3蛋白表达;做病理组织切片检查心肌损伤情况。结果芹菜素各剂量组心肌细胞凋亡率明显低于NS组(P<0.05),Api1,Api2,Api4能剂量依赖性地降低大鼠缺血/再灌注心肌细胞凋亡率;芹菜素各剂量组剂量依赖性地提高大鼠心肌缺血/再灌注的Bcl-2蛋白表达量(P<0.05)、降低大鼠心肌缺血/再灌注的Bax、Caspase-3蛋白表达量(P<0.05);芹菜素各剂量组与NS组比较,心肌组织损伤的病理学变化明显减轻(P<0.05)。结论芹菜素对缺血/再灌注心肌的保护效应可能与其抑制缺血/再灌注心肌细胞凋亡有关;芹菜素抗心肌凋亡作用的机制可能与其上调Bcl-2蛋白表达和下调Bax、Caspase-3蛋白表达有关;芹菜素能明显减轻心肌组织损伤。Aim To investigate the flavonoid apigenin on myocardial cell apoptosis and Bcl-2,Bax,Caspase-3protein expression in experimental rats with myocardial ischemia and reperfusion（ischemia/reperfusion,I/R） and to alalyze the pathological damage in myocardial tissue.Methods The myocardial ischemia-reperfusion injury model was established through occluding the left anterior descending branch of coronary artery for 45 min and removing the ligation later to reperfuse for 2 hours.Sixty-four rats were randomly divided into eight groups：normal（Normal） group,sham operation（Sham） group,saline ischemia-reperfusion（NS） group,solvent control（Sol） group,metoprolol（Meto） control group,apigenin low,medium and high dose（1 mg·kg^-1,2 mg·kg^-1,4 mg·kg^-1） treatment group（Api1,Api2,Api4）.Hearts were quickly removed after 2 h reperfusion,and myocardial cell apoptosis was marked by TUNEL;Bcl-2、Bax and Caspase-3 protein expression were tested by immunohistochemical staining method;myocardial injury degree was observed though histopathological biopsy.Results Myocardial cell apoptosis rate in apigenin groups with different doses were significantly lower than that of NS group（P〈0.05）,and dose-dependent reduction in myocardial ischemia/reperfusion was observed;Apigenin increased dose-dependently the Bcl-2 protein expression（P〈0.05） and reduced dose-dependently the Bax and Caspase-3 protein expression（P〈0.05） in rats with myocardial ischemia;Bathological damage of myocardial cells in apigenin groups with different doses were significantly lighter than that of NS group（P〈0.05）,and dose-dependent reduction was detected in myocardial ischemia/reperfusion.Conclusion The protective effect of apigenin on myocardial ischemia/reperfusion may be related to the inhibition of ischemia/reperfusion myocardial apoptosis;The mechanism of apigenin against myocardial apoptosis may involve the increased Bcl-2 protein expression and reduced Bax,Caspase-3 protein expression;Apigenin can reduce patholog

关 键 词：心肌缺血/再灌注损伤 心肌细胞凋亡 芹菜素 BCL-2蛋白 BAX蛋白 CASPASE-3蛋白 TUNEL 

分 类 号：R-332[医药卫生] R284.1