黄酒多酚减轻阿霉素心脏毒性的初步研究  

Yellow wine polyphenol compounds attenuate doxorubicin-induced cardiotoxicity

作　　者：林辉[1] 倪婷娟 张杰[1] 池菊芳[3] 项美香[2] 郭航远[1,3] LIN Hui;NI Ting-juan;ZHANG Jie;CHI Ju-fang;XIANG Mei-xiang;GUO Hang-yuan(The First Clinical Medical College, Wenzhou Medical University, Wenzhou 325000 , China;Zhejiang University School of Medicine, Hangzhou 310000 , China;Department of Cardiology, Shaoxing People’s Hospital, Shaoxing Hospital of Zhejiang University, Shaoxing 312000 , China)

机构地区：[1]温州医科大学第一临床医学院,浙江温州325000 [2]浙江大学医学院,浙江杭州310000 [3]浙江大学绍兴医院,绍兴市人民医院心内科,浙江绍兴312000

出　　处：《中国病理生理杂志》2018年第12期2132-2138,共7页Chinese Journal of Pathophysiology

基　　金：浙江省省部共建重点项目(No.WKJ-ZJ-1729);浙江省公益性技术应用研究实验动物计划(No.2017C37141);浙江省医药卫生科技项目(No.2018KY172);浙江省医药卫生省部培育计划(No.2015PYA012).

摘　　要：目的:探讨黄酒多酚化合物(YWPC)减轻阿霉素(即多柔比星,DOX)所致心脏毒性的作用及其机制。方法:将40只雄性SD大鼠随机分成4组:对照组、YWPC组、DOX组和DOX+YWPC组。干预4周后,超声心动图检测大鼠心功能;病理学染色观察心脏组织病理学改变;比色法、DHE染色、TUNEL染色和Western blot法检测心肌组织中心肌酶、氧化应激和凋亡水平的改变。结果:与对照组相比,DOX组左室射血分数(LVEF)和左室短轴缩短分数(LVFS)明显下降,而收缩期左室内径(LVIDs)和舒张期左室内径(LVIDd)明显增加;而与DOX组相比,DOX+YWPC组LVEF和LVFS增加,LVIDs和LVIDd下降(P <0. 05)。DOX组血清心肌损伤指标乳酸脱氢酶(LDH)、肌酸激酶(CK)、天冬氨酸转氨酶(AST)和心肌肌钙蛋白I(c Tn I)较对照组明显增加;而DOX+YWPC组上述指标较DOX组下降(P <0. 05)。与对照组比较,YWPC组无明显病理学改变,DOX组出现心肌纤维排列紊乱、细胞核溶解和肌纤维解体,而DOX+YWPC组上述情况明显改善。与对照组比较,DOX组活性氧簇(ROS)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)和谷胱甘肽(GSH)水平下降,丙二醛(MDA)水平增加;与DOX组相比,DOX+YWPC组上述指标均得到逆转(P <0. 05)。同时,DOX组较对照组心肌细胞凋亡水平、Bax/Bcl-2比和cleaved caspase-3水平增加,而DOX+YWPC组心肌细胞凋亡明显受到抑制(P <0. 05)。结论:黄酒多酚可以通过减少氧化应激和抑制心肌细胞凋亡拮抗阿霉素所致的心脏毒性。AIM:To investigate the effect of yellow wine polyphenol compounds(YWPC)on doxorubicin(DOX)-induced cardiotoxicity and its mechanism.METHODS:Adult male SD rats(n=40)were randomly assigned to4groups,including control group,YWPC group,DOX group and YWPC+DOX group.After4weeks of intervention,the rats were anaesthetized to measure the cardiac function using echocardiogram.The pathological changes of the heart tissues in each group were observed.The methods of colorimetry,DHE staining,TUNEL staining and Western blot were used to investigate the levels of myocardial enzymes,oxidative stress and apoptosis.RESULTS:Compared with control group,the left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)were significantly decreased,while left ventricular internal dimension at systole(LVIDs)and left ventricular internal dimension at diastole(LVIDd)were significantly decreased in the DOX group,which were notably alleviated in the DOX+YWPC group(P<0.05).In addition,the serum levels of lactate dehydrogenase,creatine kinase,aspartate aminotransferase and cardiac troponin I were significantly increased in DOX group as compared with control group.However,the levels of the above indicators were decreased in DOX+YWPC as compared with DOX group(P<0.05).Compared with control group,no significant pathological change was observed in YWPC group;however,damaged myocardial cells,nuclear lysis and disassembled muscle fiber were observed in DOX group,which were significantly alleviated in DOX+YWPC group.The levels of reactive oxygen species(ROS)production,superoxide dismutase(SOD),catalase(CAT)and glutathione(GSH)were dramatically elevated,while the level of malondialdehyde(MDA)was decreased in DOX group as compared with control group.The levels of the above-mentioned indicators were significantly reversed in DOX+YWPC group as compared with DOX group(P<0.05).Meanwhile,the apoptotic rates of cardiomyocytes,as well as the levels of Bax/Bcl-2ratio and cleaved caspase-3were significantly increased in DOX group as c

关 键 词：多柔比星 心脏毒性 黄酒多酚化合物 氧化应激 细胞凋亡 

分 类 号：R542.2[医药卫生—心血管疾病] R363[医药卫生—内科学]