大豆苷元减轻阿霉素心脏毒性的初步研究  

A preliminary study of the protective effects of daidzein against cardiotoxicity induced by doxorubicin

作　　者：奚琳 王程 马艳红 赵丹丹 张欣欣 陈松 石玥 吴金霞 XI Lin;WANG Cheng;MA Yanhong;ZHAO Dandan;ZHANG Xinxin;CHEN Song;SHI Yue;WU Jinxia(Department of Physiology,Xuzhou Medical University,Xuzhou,Jiangsu 221004,China;The First Clinical Medical School,Xuzhou Medical University;National Demonstration Center for Experimental Basic Medical Science Education,Xuzhou Medical University)

机构地区：[1]徐州医科大学生理学教研室,江苏徐州221004 [2]徐州医科大学第一临床医学院 [3]徐州医科大学基础医学国家级实验教学示范中心

出　　处：《徐州医科大学学报》2021年第7期475-479,共5页Journal of Xuzhou Medical University

基　　金：国家自然科学基金(81802529);中国博士后基金(2015M581865);江苏省博士后基金(1501053C);2019年江苏省大学生创新创业训练计划项目(201910313107H);基础医学国家级实验教学示范中心(徐州医科大学)资助项目。

摘　　要：目的通过体内外实验探讨大豆苷元(daidzein,Daid)对阿霉素(doxorubicin,Dox)引起的心脏毒性的保护作用及其机制。方法SD大鼠随机分为4组:Ctrl组、Daid组、Dox组和Daid+Dox组;干预6周后,测量大鼠心重/体重比和体长/尾长比,比色法检测血清心肌酶乳酸脱氢酶(lactate dehydrogenase,LDH)和肌酸激酶(creatine kinase,CK)活性,苏木素-伊红(H-E)染色及免疫组化染色检测大鼠心肌组织结构及Caspase-3蛋白表达水平。超氧化物阴离子荧光探针(dihydroethidium,DHE)染色法检测不同处理组大鼠心肌细胞H9C2的DHE荧光表达水平,蛋白质印迹法(Western blotting)检测凋亡蛋白Caspase-3的表达水平。结果与Ctrl组相比,Dox使大鼠心重/体重比相对增高,体长/尾长比下降,但2组比较差异无统计学意义(P>0.05)。Dox组血清心肌损伤指标LDH和CK较Ctrl组明显升高(P<0.01),而Daid+Dox组上述指标较Dox组明显下降(P<0.01)。Dox组心肌组织出现心肌纤维排列紊乱、肌纤维解体且细胞凋亡增加,而Daid+Dox组上述情况明显改善。细胞水平观察Dox处理后DHE荧光表达明显增强,Caspase-3蛋白表达增加,而Daid+Dox组上述指标均得到逆转(P<0.01)。结论大豆苷元可以通过抑制氧化应激,减少细胞凋亡拮抗阿霉素引起的心脏毒性。Objective To explore the protective effect of daidzein against myocardial injury induced by doxorubicin and related mechanisms.Methods SD rats were randomly divided into four groups:a Ctrl group,a Daid group,a Dox group and a Daid+Dox group.After intervention for six weeks,the ratio of heart weight to body weight and body length to tail length of the rats were measured.The activity of serum lactate dehydrogenase(LDH)and creatine kinase(CK)were detected by colorimetry.The structure of myocardial tissue and expression of Caspase-3 protein were detected by H-E staining and immunohistochemistry.Then,the dihydroethidium(DHE)staining was used to measure the expression of DHE fluorescence in rate cardiomyocytes H9C2 in different groups.Their levels of Caspase-3 were examined by Western blot.Results Compared with the Ctrl group,Dox treatment increased the ratio of heart weight to body weight and decreased the ratio of body length to tail length,without statistical difference between the two groups(P>0.05).The activities of LDH and CK were enhanced in the Dox group,compared with those in the Ctrl group(P<0.01),while the above indexes in the Daid+Dox group were significantly lower than those in the Dox group(P<0.01).The Dox group presented disordered and disintegrated myocardial fibers,and increased apoptosis,while the above conditions were significantly improved in the Daid+Dox group.Furthermore,the fluorescence expression of DHE and the expression of Caspase-3 protein were significantly enhanced after DOX treatment,while the above changes were reversed in the Daid+Dox group(P<0.01).Conclusions Daidzein can inhibit oxidative stress and reduce cell apoptosis against cardiotoxicity induced by doxorubicin.

关 键 词：大豆苷元 阿霉素 心脏毒性 DHE CASPASE-3 

分 类 号：R542.2[医药卫生—心血管疾病]