miRNA-330-3p/Ap2m1轴在过表达GATA-4骨髓间充质干细胞外泌体抗心肌细胞凋亡中的作用  

Role of the miRNA⁃330⁃3p/Ap2m1 axis in the overexpression of GATA⁃4 bone marrow mesenchymal stem cell exosomes in anti⁃cardiomyocyte apoptosis

作　　者：贺继刚[1] 王梓豪 李敏 谢巧丽 毛富刚[2] HE Jigang;WANG Zihao;LI Min;XIE Qiaoli;MAO Fugang(Department of Cardiovascular Surgery,the First People′s Hospital of Yunnan Province,the Affiliated Hospi-tal of Kunming University of Science and Technology,Kunming 650032,China)

机构地区：[1]云南省第一人民医院,昆明理工大学附属医院心脏大血管外科,昆明650032 [2]云南省第一人民医院,昆明理工大学附属医院心血管内科,昆明650032

出　　处：《实用医学杂志》2020年第20期2763-2768,共6页The Journal of Practical Medicine

基　　金：国家自然科学基金(编号:81460073);云南省科技厅-昆明医科大学应用基础研究联合专项[编号:2014FB089,2019FE001(-120)];云南省教育厅科学研究基金(编号:2015Z051);中国博士后科学基金(编号:2015M582764XB);成都医学院2015年度科研项目(编号:CYZ15-18);云南省医学后备人才(编号:H-201607);云南省青年拔尖人才项目。

摘　　要：目的探讨过表达GATA-4小鼠骨髓间充质干细胞(BMSC)分泌外泌体(BMSC^(GATA-4)exosome)通过miRNA-330-3p/Ap2m1轴减少心肌细胞凋亡,提高心肌梗死心功能。方法建立小鼠心梗模型,共分7组,分别经尾静脉注射BMSC^(miRNA-330-3p-mimic)-exosome、BMSC^(miRNA-330-3p-inhibitor)-exosome、BMSC^(空载体)-exosome、BMSCexosome 48 h,同时将心梗未处理组及正常小鼠作为对照组。采用心脏彩超检测各组心功能,RT-PCR检测心梗心肌细胞内miRNA-330-3p的表达,Tunel法检测各组心梗心肌细胞凋亡数量。miRNA-330-3p对应靶基因Ap2.m1、Cnot4蛋白采用Western blot法进行检测。结果BMSC^(miRNA-330-3p-mimic)-exosome组心梗心功能改善最为明显(P<0.05),其心肌细胞内miRNA-330-3p表达量最高(P<0.05)。BMSC^(miRNA-330-3p-mimic)-exosome组心肌细胞的凋亡率最低(P<0.05),BMSC^(miRNA-330-3p-mimic)-exosome组心梗心肌细胞内的Ap2.m1的表达最低(P<0.05)。结论过表达GATA-4小鼠骨髓间充质干细胞外泌体通过miRNA-330-3p/Ap2m1轴抗心肌细胞凋亡。Objective The research aimed to investigate the role of miRNA⁃330⁃3p/Ap2m1 axis in the effects of reduction of myocardial cell apoptosisand improvement of myocardial function in myocardial infarction by GATA⁃4 overexpressed⁃mouse bone marrow mesenchymal stem cell(BMSC)⁃secreted exosomes(BMSCGATA⁃4⁃exosome).Method Mouse myocardial infarction models were established and then divided into seven groups.Each mouse was injected with BMSCmiRNA⁃330⁃3p⁃mimic⁃exosome,BMSCmiRNA⁃330⁃3p⁃inhibitor⁃exosome,BMSCGATA⁃4⁃exosome,BMSCempty carrier⁃exosome,and BMSCexosome through the caudal vein for 48 hours.The untreated myocardial infarction group and normal mice were included in the control group.Cardiac color ultrasound was used to detect cardiac function in each group.The expression of miRNA⁃330⁃3p in myocardial infarction was detected by RT⁃PCR.Tunel assay was used to detect the number of apoptotic cells in myocardial tissue of myocardial infarction in each group.Western blot was used to detect the expression of the corresponding target gene Ap2m1 of miRNA⁃330⁃3p and Cnot4 protein.Results The BMSCmiRNA⁃673⁃5p⁃mimic⁃exosome group showed the most significant improvement in myocardial function in myocardial infarction(P<0.05)and the highest expression of miRNA⁃330⁃3p in cardiomyocytes(P<0.05).The cardiomyocytes in the BMSCmiRNA⁃330⁃3p⁃mimic⁃exosome group had the lowest apoptosis rate(P<0.05),and Ap2m1 in the BMSCmiRNA⁃330⁃3p⁃mimic⁃exosome+myocardial cell culture group had the lowest expression(P<0.05).Conclusion Overexpressed GATA⁃4 bone marrow⁃derived mesenchymal stem cell exosomes inhibit the expression of Ap2m1 protein against myocyte apoptosis through miRNA⁃330⁃3p.

关 键 词：miRNA-330-3p Ap2m1蛋白 GATA-4 外泌体 小鼠骨髓间充质干细胞 

分 类 号：R34[医药卫生—基础医学]