骨髓间充质干细胞来源外泌体通过microRNA-210发挥对小鼠心肌梗死的保护作用  

Bone marrow mesenchymal stem cells-derived exosomes play a protective role in myocardial infarction in mice through microRNA-210

作　　者：申怡博 李聪叶 郑南波[1] 吴冠吉[1] 郝媛媛 SHEN Yibo;LI Congye;ZHENG Nanbo;WU Guanji;HAO Yuanyuan(Xi'an Central Hospital,Xi'an 710004,China;Medical School of Yan'an University,Yan'an 716099,China;Department of Cardiology,Xijing Hospital,Air Force Medical University,Xi'an 710032,China)

机构地区：[1]西安市中心医院,陕西西安710004 [2]延安大学医学院,陕西延安716099 [3]空军军医大学西京医院心血管内科,陕西西安710032

出　　处：《空军军医大学学报》2025年第2期181-186,191,共7页Journal of Air Force Medical University

基　　金：陕西省自然科学基础研究计划项目(2023-JC-YB-788,2022JM-581);西安市博士后创新基地项目(20180823);西安交通大学自由探索与创新项目(11913223000020)。

摘　　要：目的探究骨髓间充质干细胞(BMSCs)来源的外泌体(exos)生物活性物质microRNA-210在小鼠心肌梗死(MI)后发挥的作用,评估其在MI中的潜在临床价值。方法提取BMSCs-exos并通过电镜及Western blotting进行鉴定及分析。所有小鼠随机分为4组:Sham组(只开胸不结扎)、MI组(开胸并结扎左前降支)、MI+BMSCs-exos组(结扎左前降支后注射BMSCs-exos)、MI+BMSCs-exos+microRNA-210 inhibitor组(结扎左前降支后注射转染microRNA-210抑制剂的BMSCs-exos)。左前降支冠状动脉结扎法构建小鼠MI模型后立即在梗死心肌周围行心肌内点注射exos或转染microRNA-210 inhibitor的exos。提取各组心肌组织microRNA-210并通过PCR检测其表达。超声心动图检测心脏功能。伊文思蓝染色心脏后测量MI面积。TUNEL检测心肌细胞凋亡情况。Western blotting检测心肌细胞凋亡相关蛋白的表达。结果与Sham组比较,MI组左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)明显降低,MI面积明显增多,心肌细胞凋亡水平明显增高,凋亡相关蛋白Bcl-2表达明显降低,Bax表达明显增高(P<0.05)。与MI组比较,MI+BMSCs-exos组LVEF、LVFS明显升高,MI面积明显减少,心肌细胞凋亡水平明显降低,凋亡相关蛋白Bcl-2表达明显增高,Bax表达明显降低(P<0.05)。与MI+BMSCs-exos组比较,MI+BMSCs-exos+microRNA-210 inhibitor组LVEF、LVFS明显降低,MI面积明显增多,心肌细胞凋亡水平明显增高,凋亡相关蛋白Bcl-2表达明显降低,Bax表达明显增高(P<0.05)。结论BMSCs来源的exos通过microRNA-210减轻细胞的凋亡,从而提高MI后小鼠的心功能,减少小鼠的MI面积,对小鼠MI起到了一定的保护作用。Objective To investigate the role of microRNA-210,a bioactive substance of exosomes(exos) derived from bone marrow mesenchymal stem cells(BMSCs),in mice after myocardial infarction(MI) to evaluate its potential clinical value in MI.Methods BMSCs-exos were extracted,identified and analyzed by electron microscopy and Western blotting.All mice were randomly divided into four groups:Sham group(only thoracotomy without ligation),MI group(thoracotomy and left anterior descending artery ligation),MI + BMSCs-exos group(left anterior descending artery ligation followed by injection of BMSCs-exos),MI + BMSCs-exos + microRNA-210 inhibitor group(left anterior descending artery ligation followed by injection of BMSCs-exos transfected with microRNA-210 inhibitor).After the mouse model of MI was established by left anterior descending coronary artery ligation,exos or exos transfected with microRNA-210 inhibitor were infused intramuscularly around the infarcted myocardium immediately.MicroRNA-210 was extracted from myocardial tissues of each group and its expression was detected by PCR.The cardiac function was tested by echocardiography.The MI area was measured after Evans blue staining of the heart.The apoptosis of cardiomyocytes in each group was detected by TUNEL.The expression of apoptosis-related proteins in cardiomyocytes was detected by Western blotting.Results Compared with Sham group,left ventricular ejection fraction(LVEF) and left ventricular fractional shortening(LVFS) in MI group were significantly decreased,the MI area was significantly increased,the apoptosis level of cardiomyocytes was significantly increased,the apoptosis-related protein Bcl-2 expression was significantly decreased,and Bax expression was significantly increased(P<0.05).Compared with MI group,LVEF and LVFS in MI + BMSCs-exos group were significantly increased,MI area was significantly decreased,myocardial apoptosis level was significantly decreased,apoptosis-related protein Bcl-2 expression was significantly increased,and Bax expression was signi

关 键 词：外泌体 microRNA-210 心肌梗死 细胞凋亡 

分 类 号：R542.22[医药卫生—心血管疾病]