养心康片通过(Akt/AMPK)-mTOR通路抑制心梗后心力衰竭模型兔心肌细胞凋亡的机制  

Mechanism of Yangxinkang Tablet in Inhibiting Cardiomyocyte Apoptosis in Rabbit with Heart Failure After Myocardial Infarction Through Akt/AMPK-mTOR Pathway

作　　者：任培华 王鹏 廖东江 李振球 朱汉平 胡素珍 REN Pei-hua;WANG Peng;LIAO Dong-jiang;LI Zhen-qiu;ZHU Han-ping;HU Su-zhen(The First Affiliated Hospital of Guangzhou Medical University,Guangzhou 510120,China)

机构地区：[1]广州医科大学附属第一医院

出　　处：《中国实验方剂学杂志》2018年第16期124-130,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家自然科学基金面上项目(81673902);广州市教育局项目(1201411088);广东省中医药局项目(20142093)

摘　　要：目的：观察养心康片通过[蛋白激酶B（protein kinase B,Akt）/腺苷酸活化蛋白激酶（AMP-activated kinase,AMPK）]-乳动物雷帕霉素靶蛋白（mammalian target of rapamycin,mTOR）通路对心梗后心力衰竭模型兔心肌细胞凋亡的影响。方法：应用结扎冠脉的方法建立心梗后心力衰竭兔模型,随机分为模型组,养心康组,AMPK抑制剂组（10 mg·kg^-1Compound C腹腔注射,每日2次）,Akt抑制剂组（10 mg·kg^-1casodex灌胃,每日2次）和mTOR抑制剂组（0.5 mg·kg^-1rapamycin灌胃,每日2次）,并设立正常组,每组5只,共30只。给予养心康片0.51 g·kg^-1灌胃,每日1次,正常组和模型组给予等体积的蒸馏水灌胃,共4周。心脏彩超检测心功能,蛋白免疫印迹法（Western blot）检测心肌B细胞淋巴瘤/白血病-2（Bcl-2）,Bcl-2相关X蛋白（Bax）蛋白表达,原位末端凋亡法（TUNEL）检测心肌细胞凋亡。结果：与正常组比较,模型组的左室射血分数（LVEF）值降低（P〈0.01）,Bcl-2,Bax蛋白表达量增高（P〈0.05,P〈0.01）,Bcl-2/Bax降低（P〈0.01）,心肌细胞凋亡率升高（P〈0.01）;与模型组比较,养心康组的LVEF值升高（P〈0.01）,Bax蛋白表达量降低（P〈0.01）,Bcl-2/Bax升高（P〈0.01）,心肌细胞凋亡率降低（P〈0.01）。与抑制剂各组比较,养心康组的LVEF值升高（P〈0.01）,Bcl-2/Bax升高（P〈0.01）,心肌细胞凋亡率降低（P〈0.01）。结论：养心康片可通过干预（Akt/AMPK）-mTOR通路调控心肌细胞Bcl-2,Bax蛋白表达水平减少心肌细胞凋亡,改善心梗后心衰模型的心脏功能。Objective： To observe the effect of Yangxinkang tablet on cardiomyocyte apoptosis in rabbit with heart failure after myocardial infarction through protein kinase B（Akt）/AMP-activated kinase（AMPK）-the mammalian target of rapamycin（mTOR） pathway. Method： The rabbit model of heart failure was established through ligation of coronary artery. A total of 30 experimental animals were randomly divided into model group,Yangxinkang group,AMPK inhibitor group（10 mg·kg^-1 Compound C,intraperitoneal injection,2 times a day）,Akt inhibitor group（10 mg·kg^-1 casodex,intragastric administration,2 times a day） and mTOR inhibitor group（0. 5 mg·kg^-1 rapamycin,intragastric administration,2 times a day）,and a blank control group was also set up,with 5 in each group. Yangxinkang tablet（0. 51 g ·kg-1） were intragastrically administered once a day. Blank control group and experimental groups were given the equivalent volume of distilled water for 4 weeks. Heart function was detected by color Doppler ultrasound,Bcl-2 and Bax protein expressions were detected by Western blot,and cardiomyocyte apoptosis was detected by Td T-mediated DUTP nick end labeling（TUNEL）. Result：Compared with the blank control group,the LVEF value of the model group decreased（P〈0. 01）,the expressions of Bcl-2 and Bax protein increased（P〈0. 05,P〈0. 01）,the Bcl-2/Bax ratio decreased（P〈0. 01）,and cardiomyocyte apoptosis rate was increased（P〈0. 01）. Compared with the model group,the LVEF value of the Yangxinkang group was increased（P〈0. 01）,the expression of Bax protein was decreased（P〈0. 01）,the Bcl-2/Bax ratio was increased（P〈0. 01）,and the cardiomyocyte apoptosis rate was decreased（P〈0. 01）.Compared with each inhibitor groups,the LVEF value of Yangxinkang group was increased（P〈0. 01）,Bcl-2/Bax ratio was increased（P〈0. 01）,and the cardiomyocyte apoptosis rate was decreased（P〈0. 01）. Conclusion：Yangxinkang tablet can regulate the expressions of Bcl-2 and Bax

关 键 词：养心康片 心力衰竭 蛋白激酶B(protein KINASE B Akt)/腺苷酸活化蛋白激酶(AMP-activated kinase AMPK)-乳动物雷帕霉素靶蛋白(mammalian target of rapamycin mTOR)通路 心功能 心肌细胞凋亡 

分 类 号：R22[医药卫生—中医基础理论] R24[医药卫生—中医学]