内皮特异性miR-342-5p敲除致小鼠内皮损伤和心血管功能紊乱  

Endothelium-specific miR-342-5p Knockout Induces Vascular Endothelial Dysfunction and Cardiovascular Dysfunction in Mice

作　　者：李纪君 谭延振 杨红燕 周嘉恒 丁昕 李宸涵 张鹏飞[1] 吴方琴 高峰[1] 李敏[1] 张星[1] LI Ji-jun;TAN Yan-zhen;YANG Hong-yan;ZHOU Jia-heng;DING Xin;LI Chen-han;ZHANG Peng-fei;WU Fang-qin;GAO Feng;LI Min;ZHANG Xing(School of Aerospace Medicine,Air Force Medical University,Xi'an,Shaanxi,710032,China;Department of Ultrasound,PLA 66284 Hospital,Beijing,100039,China;School of Life Sciences,Northwest University,Xi'an,Shaanxi,710127,China)

机构地区：[1]中国人民解放军空军军医大学航空航天医学系,陕西西安710032 [2]中国人民解放军66284医院超声科,北京100039 [3]西北大学生命科学院,陕西西安710127

出　　处：《现代生物医学进展》2022年第8期1408-1412,1449,共6页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(31871146,32071169);陕西省自然科学基金项目(2020JQ-442)。

摘　　要：目的:我们前期研究发现有氧运动促进内皮细胞等分泌mi R-342-5p,mi R-342-5p通过外泌体富集至心肌细胞后发挥心脏保护作用。本研究的主要目的是明确内皮来源的mi R-342-5p在心血管功能调控中的作用。方法:我们构建了内皮特异性mi R-342-5p敲除小鼠,通过心脏超声检测和血管收缩舒张功能检测观察了该小鼠心血管功能的变化;培养血管内皮细胞,通过对细胞存活率检测、相关蛋白的表达检测等方法对mi R-342-5p发挥心血管保护作用的机制进行探究。结果:内皮mi R-342-5p敲除致小鼠运动能力降低、心脏收缩功能不变,但舒张功能紊乱。且内皮mi R-342-5p敲除致小鼠血管口径变小、微血管密度降低和血管内皮功能紊乱。内皮mi R-342-5p敲除致小鼠心血管功能紊乱的机制与其引起的内皮细胞损伤有关。敲低mi R-342-5p致内皮细胞中caspase 9水平增加,引起内皮细胞活性降低和凋亡增加。结论:这些结果进一步证实了内皮细胞来源的mi R-342-5p在心血管功能中的重要作用,提示mi R-342-5p在防治心血管疾病中的潜在应用。Objective:We previously found that aerobic exercise protects the heart through secreting mi R-342-5p from endothelial cells and others.The aim of the study is to test the role of mi R-342-5p in cardiovascular function and its underlying mechanism.Methods:An endothelium-specific mi R-342-5p knockout mice model was established.The echocardiography and vasodilation in isolated aortas were detected.Cell viability and apoptosis-related protein contents in endothelial cells were tested to explore the underlying mechanism.Results:Endothelium-specific mi R-342-5p knockout decreased the exercise capacity,and cardiac diastolic function,although the cardiac systolic function was unchanged.In addition,it decreased the capillary density in the heart and induced endothelial dysfunction.The cardiovascular dysfunction induced by mi R-342-5p knockout may attribute to the endothelial injury induced by mi R-342-5p deficiency in endothelial cells.Knockdown of mi R-342-5p increased the content of caspase 9,decreased the cell viability and promoted apoptosis in cultured endothelial cells.Conclusions:These results suggested that endothelium-derived mi R-342-5p plays an important role in cardiovascular function,and highlights the potential of mi R-342-5p in treatment of cardiovascular disease.

关 键 词：mi R-342-5p 内皮细胞 心血管功能 凋亡 

分 类 号：R-33[医药卫生] R540.47