摘要
目的探讨二甲基乙二酰基甘氨酸(DMOG)预处理对骨髓间充质干细胞(MSC)来源的外泌体(exosome)在心肌保护机制方面生物学特性的影响。方法分离及鉴定间充质干细胞来源的exosome,比较DMOG预处理后MSCs分泌的exosome(ExoDMOG)与常规处理来源的exosome(Exo)对小鼠心肌梗死后心肌保护、体外内皮细胞血管形成能力及心肌细胞抗凋亡能力的影响。结果DMOG预处理后MSCs分泌的exosome明显改善小鼠心肌梗死后心功能并延长生存期,在体外实验中拥有更佳的促血管新生能力及心肌细胞保护能力。DMOG预处理的exosome中miR-210表达水平明显上升,在体外实验中miR-210 mimic转染到受体细胞中拥有与ExoDMOG相似的生物学作用;体内实验发现,加入miR-210的抑制剂(antogomiR-210)后明显削弱了ExoDMOG对促血管新生、心肌细胞保护的作用。结论DMOG预处理后MSCs来源的exosome拥有更佳的促血管生成能力及心肌细胞保护作用,可能通过miR-210来发挥生物学作用。
Objective To investigate the effects of dimethyloxalyglycine(DMOG)pretreatment on biological characteristics of myocardial protection by exosome(MSC-Exo)derived from MSCs(mesenchymal stem cells).Methods Exosome derived from MSCs was isolated and identified,and the capacity of improving cardiac function after myocardial infarction(MI),pro-angiogenesis and anti-apoptosis were compared between exosome(ExoDMOG)secreted by MSCs after DMOG treatment and exosome(Exo)after conventional treatment.Results DMOG preconditioned MSCsExo significantly improved cardiac function and prolonged survival after MI in mice,and exerted better pro-angiogenesis and cardioprotection ability in vitro.The expression level of miR-210 in DMOG preconditioned exosome was significantly increased,and miR-210 mimic exerted into recipient cells had similar biological function as ExoDMOGin vitro.However,the pro-angiogenesis and cardioprotection ability of ExoDMOGwas significantly weakened by adding miR-210 inhibitor,antogomiR-210,in vivo.Conclusion DMOG preconditioned MSC-Exo has superior ability of cardio-protection and pro-angiogenesis,which might due to the biological effects of miR-210.
作者
王香云
张东伟
WANG Xiangyun;ZHANG Dongwei(Department of Neurology,the First People's Hospital of Huzhou,Huzhou,Zhejiang 313000,China)
出处
《重庆医学》
CAS
2019年第24期4151-4156,共6页
Chongqing medicine
基金
国家自然科学基金项目(81570251)
浙江省医药卫生科技计划项目(2017KY639)
