卵泡抑素样蛋白1对阿霉素所致小鼠急性心肌损伤的改善作用及其机制  

Improvement effect of follistatin-like 1 on doxorubicin-induced acute myocardial injury in mice and its mechanism

作　　者：赵荫涛[1] 杨莹莹 张相钦 郑璐[1] 徐亚威 杨海波[1] 刘源[1] ZHAO Yintao;YANG Yingying;ZHANG Xiangqin;ZHENG Lu;XU Yawei;YANG Haibo;LIU Yuan(Department of Cardiology,First Affiliated Hospital,Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院心血管内科,河南郑州450052

出　　处：《吉林大学学报（医学版）》2023年第3期565-572,共8页Journal of Jilin University：Medicine Edition

基　　金：国家自然科学基金项目(81600189);河南省科技厅科技攻关计划项目(182102310099)。

摘　　要：目的:探讨卵泡抑素样蛋白1(FSTL1)对阿霉素(DOX)诱导的小鼠急性心肌损伤的保护作用,并阐明其相关机制。方法:80只C57BL/6J小鼠采用单次腹腔内注射DOX建立小鼠急性心肌损伤模型,小鼠按DOX不同剂量(0、5、10、15和20 mg·kg^(-1))分为5组(n=8);按不同干预时间(0、0.5、1.0、2.0和3.0d)分为5组(n=8)。另取32只小鼠随机分为生理盐水组、FSTL1组、DOX组和DOX+FSTL1组。测定各组小鼠心脏超声心动图和血流动力学指标,酶联免疫吸附测定(ELISA)法检测各组小鼠血清中肿瘤坏死因子α(TNF-α)、N端脑钠肽体(NT-proBNP)和肌钙蛋白T(cTn-T)水平,氧化应激试剂盒检测各组小鼠心肌组织中超氧化物歧化酶(SOD)活性和丙二醛(MDA)、4-羟基壬烯醛(4-HNE)及15-F_(2t)-isoprostane水平,实时荧光定量PCR(RT-qPCR)法检测各组小鼠心肌组织中FSTL1 mRNA表达水平,Western blotting法检测各组小鼠心肌组织中核因子E2相关因子2(Nrf2)和FSTL1蛋白表达水平。结果:与生理盐水组比较,DOX组和DOX+FSTL1组小鼠左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)、左心室收缩压(LVSP)、左心室内压最大上升速率(+dP/dt_(max))和左心室内压最大下降速率(-dP/dt_(max))降低(P<0.05),心率(HR)、左心室舒张末期容积(LVEDV)和左心室舒张压(LVDP)升高(P<0.05);与DOX组比较,DOX+FSTL1组小鼠LVEF、+dP/dt_(max)和-dP/dt_(max)升高(P<0.05),LVEDV降低(P<0.05)。与生理盐水组比较,DOX组和DOX+FSTL1组小鼠血清中TNF-α、NT-proBNP和cTn-T水平升高(P<0.05);与DOX组比较,DOX+FSTL1组小鼠血清中NT-proBNP和cTn-T水平降低(P<0.05)。与生理盐水组比较,DOX组小鼠心肌组织中SOD活性降低(P<0.05),MDA、4-HNE和15-F_(2t)-isoprostane水平升高(P<0.05),DOX+FSTL1组小鼠心肌组织中15-F_(2t)-isoprostane水平升高(P<0.05);与DOX组比较,DOX+FSTL1组小鼠心肌组织中SOD活性升高(P<0.05),MDA、4-HNE和15-F_(2t)-isoprostane水平降低(P<0.05)。与0 mg·kg^(-1)DOX组比较,随着DOX�Objective:To discuss the protective effectof follistatin-like 1(FSTL1)on doxorubicin(DOX)-induced acute myocardial injury of the mice,and to clarify its related mechanism.Methods:A total of 80 C57BL/6J mice were used to establish the acute myocardial injury models by intraperitoneal injection of DOX for one time.The mice were divided into 5 groups(n=8)according to the different doses(0,5,10,15,and 20 mg·kg^(-1))of DOX,and didvided into 5 groups(n=8)according to the different intervention time(0,0.5,1.0,2.0,and 3.0 d).The other 32 mice were randonly divided into normal saline group,FSTL1 group,DOX group,and DOX-FSTL1 group.The echocardiographic and hemodynamic indexes of the mice in various groups were detected;enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of tumor necrosis factor-α(TNF-α),N-terminal pro-brain natriuretic peptide(NT-proBNP)and cardiae troponin-T(cTn-T)in serum of the mice in various groups;the activities of superoxide dismutase(SOD),the levels of malondialdehyde(MDA),4-hydroxynonenal(4-HNE)and 15-F_(2t) isoprostane in myocardium tissue of the mice in various groups were detected by oxidative stress kit;the expression levels of FSTL1 mRNA in myocardium tissue of the mice in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)method;the expression levels of nuclear factor E2 related factor 2(Nrf2)and FSTL1 proteins in myocardium tissue of the mice in various groups were detected by Western blotting method.Results:Compared with normal saline group,the left ventricular ejection fraction(LVEF),left ventricular fraction shortening(LVFS),left ventricular systolic pressure(LVSP),maximum rise rate of left ventricular pressure(+dP/dt_(max)),and maximum drop rate of left ventricular pressure(-dp/dt_(max))of the mice in DOX group and DOX+FSTL1 group were significantly decreased(P<0.05),and the heart rate(HR),left ventricular end-diastolic volume(LVEDV),and left ventricular diastolic pressure were increased(P<0.05);compared with DOX group,the LVEF,+

关 键 词：卵泡抑素样蛋白1 阿霉素 心肌损伤 心脏毒性 氧化应激 

分 类 号：R542.2[医药卫生—心血管疾病]