丹参多酚酸盐抑制氧化应激减轻阿霉素诱导的心脏毒性研究  

Study on the inhibition of oxidative stress by salvia polyphenolates to alleviate adriamycin-induced cardiotoxicity

作　　者：张旼旼 黄新宇 戴慧 ZHANG Minmin;HUANG Xinyu;DAI Hui(Department of Radiotherapy,Affiliated Hangzhou Cancer Hospital,Zhejiang University School of Medicine,Hangzhou 310002,Zhejiang,China;Department of Medical Oncology,Affiliated Hangzhou Cancer Hospital,Zhejiang University School of Medicine,Hangzhou 310002,Zhejiang,China)

机构地区：[1]浙江大学医学院附属杭州市肿瘤医院放疗科,浙江杭州310002 [2]浙江大学医学院附属杭州市肿瘤医院肿瘤内科,浙江杭州310002

出　　处：《中国现代医生》2023年第26期119-124,共6页China Modern Doctor

基　　金：杭州市农业与社会发展科研项目(20180533B64)。

摘　　要：目的探究丹参多酚酸盐(salvianolate,SAL)对阿霉素(adriamycin,ADM)诱导心脏毒性的保护作用及调控机制。方法采用随机数字表法将40只小鼠分为对照组、ADM组、等效剂量丹参多酚酸盐(equivalent dose of salvianolate,ESAL)组和高剂量丹参多酚酸盐(high-dose salvianolate,HSAL)组,每组10只,超声检测心脏结构和功能,测量小鼠体质量和心脏重量计算心脏体质量比,苏木精–伊红染色观察心脏组织形态,TUNEL检测法检测心脏组织凋亡,ELISA法检测小鼠血清中乳酸脱氢酶(lactate dehydrogenase,LDH)、天冬氨酸氨基转移酶(aspartate aminotransferase,AST)、B型钠尿肽(B-type natriuretic peptide,BNP)、丙二醛(malondialdehyde,MDA)及超氧化物歧化酶(superoxide dismutase,SOD)的含量水平。将小鼠心肌细胞仍分为上述四组,每组均设3个重复孔,每个实验重复3次。CCK-8和流式细胞术检测心肌细胞活性和凋亡;ELISA法检测心肌细胞上清液中LDH、AST、MDA和SOD的含量。结果SAL可减轻ADM诱导的心肌肥厚、改善射血分数和降低心脏体质量比(P<0.05),减轻心肌组织纤维化,减少组织细胞发生凋亡(P<0.05);降低了ADM诱导的小鼠血清中LDH、AST、BNP和MDA水平(P<0.05),升高了SOD的水平(P<0.05);SAL能提高ADM抑制的心肌细胞活性(P<0.05)、减少细胞凋亡(P<0.05),降低了小鼠心肌细胞中LDH、AST和MDA水平(P<0.05),升高了SOD的水平(P<0.05)。结论SAL可能通过抑制氧化应激发挥对ADM诱导的心脏毒性的保护作用。Objective To investigate the protective effect and regulatory mechanism of salvianolate(SAL)on adriamycin(ADM)-induced cardiotoxicity.Methods A total of 40 mice were randomly divided into control group,ADM group,equivalent dose of salvianolate(ESAL)group,high-dose salvianolate group(HSAL)group,with 10 rats in each group.The heart structure and cardiac function were detected by ultrasound,the weight and heart weight of mice were measured to calculate the heart weight ratio,and the morphology of heart tissue was observed by HE staining,TUNEL assay to detect cardiac tissue apoptosis,ELISA method was used to detect the contents of lactate dehydrogenase(LDH),aspartate aminotransferase(AST),B-type natriuretic peptide(BNP),malondialdehyde(MDA)and superoxide dismutase(SOD)in mouse serum.The mouse primary cardiomyocytes were still divided into the above 4 groups,with each group consisting of three repeated wells,and each experiment was repeated three times.the cardiomyocyte activity and apoptosis were detected by CCK-8 and apoptosis kit;ELISA method was used to detect LDH,AST,MDA and SOD content in cardiomyocyte culture medium.Results SAL can reduce ADM induced myocardial hypertrophy,improve ejection fraction and reduce heart weight ratio(P<0.05),reduce myocardial fibrosis,and reduce apoptosis of tissue cells(P<0.05).It decreased the levels of LDH,AST,BNP and MDA in serum of mice induced by ADM(P<0.05),and increased the level of SOD(P<0.05).SAL can increase the activity of cardiomyocytes inhibited by ADM(P<0.05),reduce apoptosis(P<0.05),decreased the level of LDH,AST and MDA in mouse cardiomyocytes(P<0.05),increased the level of SOD(P<0.05).Conclusion SAL may play a protective role on ADM induced cardiotoxicity by inhibiting oxidative stress.

关 键 词：丹参多酚酸盐 阿霉素 心脏毒性 

分 类 号：R273[医药卫生—中西医结合]