黄芪甲苷通过抑制MerTK缓解阿霉素引起的心脏毒性  

Study on astragalosideⅣalleviating the cardiotoxicity caused by doxorubicin by inhibiting MerTK

作　　者：王雪丽 陈亚男 黄厚芹 刘岳鹏 许瑾[3] 何学明[4] WANG Xue-li;CHEN Ya-nan;HUANG Hou-qin;LIU Yue-peng;XU Jin;HE Xue-ming(Department of Geriatrics,Lianyungang Oriental Hospital Affiliated to Bengbu Medical College,Lianyungang Jiangsu 222042;Institute of Medical Sciences of Xuzhou,Xuzhou Jiangsu 221000;Department of Basic Medicine,Kangda College of Nanjing Medical University,Lianyungang Jiangsu 222000,China;Conversion Medical Center,Lianyungang Oriental Hospital Affiliated to Bengbu Medical College,Lianyungang Jiangsu 222042)

机构地区：[1]蚌埠医学院附属连云港市东方医院老年医学科,江苏连云港222042 [2]江苏省徐州市医学科学研究所,221000 [3]南京医科大学康达学院,江苏连云港222042 [4]蚌埠医学院附属连云港市东方医院转化医学中心,江苏连云港222042

出　　处：《蚌埠医学院学报》2021年第6期717-721,共5页Journal of Bengbu Medical College

基　　金：江苏省连云港市科技局社会发展基金项目(SF2016);江苏省海燕人才计划(KD2019lyghy001);蚌埠医学院研究生科研创新计划项目(Byycx1930)。

摘　　要：目的:探讨黄芪甲苷对阿霉素诱导的心肌损伤的作用及机制。方法:6周龄ICR雄性小鼠随机分为对照组、阿霉素组、阿霉素+黄芪甲苷组。对照组给予单次腹腔注射0.9%氯化钠溶液,其余组均给予单次腹腔注射20 mg/kg阿霉素造模。阿霉素+黄芪甲苷80 mg/kg组行每天1次黄芪甲苷80 mg/kg灌胃,其余组给予0.5%羧甲基纤维素钠灌胃,持续至造模第10天。于第10天进行心脏超声检测小鼠心肌功能指标射血分数和缩短分数,进行心电图测试监测小鼠心率;于第10天取小鼠血清和心脏组织采用Masson染色法检测心肌组织结构的变化,使用全自动血清生化仪检测血清中乳酸脱氢酶(LDH)、肌酸激酶(CK-MB)水平,采用ELISA法检测血清中白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)水平,以Western blotting检测心肌中Mer酪氨酸激酶(MerTK)蛋白表达。结果:与对照组相比,阿霉素组小鼠心率明显减慢、QT间期明显延长(P<0.01);心脏射血分数和缩短分数均明显降低(P<0.01);心肌酶CK-MB和LDH含量均明显增加(P<0.01);p-MerTK的蛋白表达明显增加(P<0.01);IL-1β、IL-6、TNF-α水平均明显升高(P<0.01);小鼠心肌细胞间质出现严重纤维化。与阿霉素组相比,阿霉素+黄芪甲苷80 mg/kg组小鼠QT间期明显缩短(P<0.01),心率改善几乎达到正常水平;心脏射血分数和缩短分数下降程度明显改善(P<0.01);CK-MB和LDH含量均明显降低(P<0.01);p-MerTK的表达水平明显下降(P<0.01);IL-1β、IL-6、TNF-α水平均明显下降(P<0.01);小鼠心肌纤维化面积明显减少。结论:黄芪甲苷可能通过抑制MerTK裂解减轻心肌损伤,减轻阿霉素诱导的心脏毒性。Objective:To investigate the effects and mechanism of astragalosideⅣon the doxorubicin-induced myocardial injury.Methods:The 6-week-old ICR male mice were randomly divided into the control group,doxorubicin group,doxorubicin+AstragalosideⅣgroup.The control group was given a single intraperitoneal injection of 0.9%sodium chloride solution,and the other groups were given a single intraperitoneal injection of 20 mg/kg doxorubicin for modeling.The doxorubicin+astragalosideⅣ80 mg/kg group were given astragalosideⅣonce a day by gavage,and the other groups were given a solvent(0.5%sodium carboxymethyl cellulose)by gavage for 10 days.On the 10th day,the mice′s myocardial function(ejection fraction and fractional shortening)were detected using the echocardiography,and the heart rate of mice were monitored by the electrocardiogram test.On the 10th day,the serum and heart tissue of mice were collected,and the changes in the myocardial tissue structure were detected using Masson staining,and the levels of lactate dehydrogenase(LDH)and creatine kinase(CK-MB)were detected using biochemistry.The serum levels of interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in mice were examined using ELISA,and the protein levels of Mer tyrosine kinase(MerTK)in the myocardium were detected using Western blotting.Results:Compared with the control group,the heart rate and QT interval were significantly slower(P<0.01),the cardiac ejection fraction and fractional shortening significantly decreased(P<0.01),the contents of myocardial enzyme CK-MB and LDH significantly increased(P<0.01),the protein expression lev el of p-MerTK significantly increased(P<0.01),the levels of IL-1β,IL-6 and TNF-αsignificantly increased(P<0.01),and there was severe fibrosis in the interstitium of mouse myocardial cells in adriamycin group.Compared with the doxorubicin group,the QT interval was significantly shortened(P<0.01),the heart rate was improved almost to the normal level,the decreasing of cardiac ejection fraction and fra

关 键 词：阿霉素 心脏毒性 黄芪甲苷 

分 类 号：R979.14[医药卫生—药品]