心肌细胞外泌体纳米囊泡介导p53调节自噬保护心肌梗死

IF 2.9 4区 医学 Q1 Medicine Journal of biomedical nanotechnology Pub Date : 2023-08-01 DOI:10.1166/jbn.2023.3646
M. Fan, Fei Xie, Jianfeng Li, Junquan Li, Ting Liang
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引用次数: 0

摘要

本研究探讨心肌细胞外泌体纳米囊泡对心肌梗死的保护机制。通过TdT介导的dUTP缺口末端标记(TUNEL)测量酶活性并评估大鼠心肌细胞的凋亡,同时通过彩色多普勒超声心动图分析心肌功能。此外,氯化三苯基四氮唑(TTC)染色评估心肌缺血。BMSC与原代心肌细胞共培养,然后通过透射电子显微镜测量心肌组织的自噬和外泌体形态,并通过蛋白质印迹测量蛋白质表达。成功分离了骨髓间充质干细胞分泌的外泌体。模型组LDH、CK、CK-MB活性、心肌细胞凋亡率、LVESD、LVEDP、心肌梗死面积、自噬泡占细胞面积和p53表达均高于对照组(P<0.05),外泌体组低于模型组。此外,LVEF、LVFS和LVSP在模型组较低,在外泌体组较高(P<0.05)。此外,还发现了直径为60–90 nm的外泌体样囊泡。此外,PKH-26染色显示心肌细胞可以很好地摄取外泌体。心肌损伤显著促进自噬激活。此外,心肌梗死大鼠心肌细胞凋亡率和心肌缺血面积降低,心功能改善。
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Cardiomyocyte Exosomal Nanovesicles Mediating p53 to Regulate Autophagy and Protect Myocardial Infarction
This study explores the protective mechanism of cardiomyocyte exosome nanovesicles on myocardial infarction. Enzyme activity was measured and apoptosis of rat cardiomyocytes was assessed by TdT-mediated dUTP Nick-End Labeling (TUNEL) along with analysis of myocardial function by color Doppler echocardiogram. In addition, triphenyl tetrazolium chloride (TTC) staining evaluated the myocardial ischemia. BMSCs were co-cultured with primary cardiomyocytes followed by measuring autophagy and exosome morphology of myocardial tissue by transmission electron microscope and protein expression by Western blot. Exosomes secreted by Bone marrow mesenchymal stem cells (BMSCs) were successfully isolated. LDH, CK, CK-MB activity, cardiomyocyte apoptosis rate, LVESD, LVEDD, LVEDP, myocardial infarction area, cell area occupied by autophagic vesicles and p53 expression in model group were higher than control group (P <0.05) and they were lower in exosome group than model group. In addition, LVEF, LVFS, and LVSP were lower in model group and higher in exosome group (P <0.05). Model group showed significantly promoted autophagy activation and autophagosome formation, which were inhibited by cardiomyocyte exosomes. Moreover, exosome-like vesicles were found with a diameter of 60–90 nm. Furthermore, PKH-26 staining showed that cardiomyocytes could uptake exosomes well. Myocardial injury significantly promotes autophagy activation. Moreover, the apoptosis rate of cardiomyocytes and the area of myocardial ischemia were reduced and the cardiac function of rats with myocardial infarction was improved.
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CiteScore
4.30
自引率
17.20%
发文量
145
审稿时长
2.3 months
期刊介绍: Information not localized
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