巨噬细胞来源外泌体介导心肌梗塞后心脏重塑的作用研究  

Effects of Macrophage-derived Exosomes on the Cardiac Remodeling after Myocardial Infarction

作　　者：蔡利栋 吴晓宇 丁羽 巩超 刘少稳[1] CAI Li-dong;WU Xiao-yu;DING Yu;GONG Chao;LIU Shao-wen(Department of cardiology,Shanghai general hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,201600,China)

机构地区：[1]上海交通大学附属第一人民医院心内科,上海201600

出　　处：《现代生物医学进展》2020年第5期808-812,837,共6页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(81970273)。

摘　　要：目的:研究活化的巨噬细胞来源外泌体在心肌梗塞后心脏重塑中的作用。方法:采用超高速离心分离提取溶血磷脂酸作用下巨噬细胞来源的外泌体,将其与心脏成纤维细胞共同孵育48小时,利用Edu细胞增殖实验、Transwell实验及免疫荧光等方法检测溶血磷脂酸刺激(LPS)下巨噬细胞来源外泌体对心脏成纤维细胞的增殖、迁移以及分化的影响。选取正常C57雄性小鼠32只,根据其是否结扎左侧冠状动脉前降支及是否进行心脏原位外泌体注射,将实验小鼠随机分为:正常组,假手术组,心梗+空白外泌体组及心梗组+LPS刺激外泌体组。手术完成4周后行心脏超声、Masson染色以检测各组实验小鼠心功能状态及心脏纤维化程度。结果:在细胞实验中,LPS刺激的巨噬细胞来源外泌体可以显著增加心脏成纤维细胞的增殖、迁移以及分化能力;在动物实验中,相对于正常组、假手术组及心梗+空白-外泌体组,心梗+LPS-外泌体组小鼠的左心室射血分数及短轴收缩率显著下降,左心室舒张末及收缩末内径显著增加。Masson染色检测提示心肌梗塞+LPS-外泌体组小鼠心脏纤维化程度显著高于其余三组。结论:活化的巨噬细胞来源的外泌体可以显著加速心梗后心脏重塑的进程。Objective: To explore the role of macrophage-derived exosomes on the cardiac remodeling following myocardial infarction(MI) and the possible molecular mechanism. Methods: Exosomes isolated from supernatant of macrophage stimulated by LPS were incubated with cardiac fibroblasts for 48 h, and then the ability of cardiac fibroblasts proliferation, migration and differentiation were detected by Edu assay, Transwell assay and immunofluorescence assay. Additionally, thirty-two male mice were divided into 4 groups as Control group, Sham group, MI+NC-Exos group and MI+LPS-Exos group according to whether the left anterior descending coronary artery was ligated and exosomes were injected in the tissue of heart. After four weeks, cardiac function and the extent of cardiac fibrosis were assessed by echocardiography and Masson’s trichrome staining. Results: Exosomes derived from macrophage stimulated by LPS significantly elevated the ability of cardiac fibroblasts migration, proliferation and differentiation;Additionally, Echocardiographic analysis showed that exosomes derived from macrophage stimulated by LPS induced deterioration of cardiac dysfunction post-MI, as indicated by the smaller fractional shortening(FS%) and ejection fraction(EF%), and the larger left ventricular end diastolic diameter(LVEDD) and left ventricular end systolic diameter(LVESD). Similarly, a more remarkable intestinal fibrosis in MI+LPS-Exos group were detected than in other three groups as assessed by Masson’s trichrome staining. Conclusions: Activated Macrophage-derived exosomes promotes cardiac remodeling following MI.

关 键 词：心肌梗塞 巨噬细胞 心脏纤维化 外泌体 

分 类 号：R-33[医药卫生] R542.22