脂肪间充质干细胞外泌体调控心脏成纤维细胞自噬和NLRP3炎症小体平衡抑制心肌梗死后不良心室重塑  

Adipose derived mesenchymal stem cell exosomes inhibit adverse ventricular remodeling after myocardial infarction by regulating autophagy and NLRP3 inflammasomes balance of cardiac fibroblasts

作　　者：王建军 李晶[2] 马旭明[2] 万招飞 朱滨 刘亚萍 郭向前 潘吉平 樊艳[2] WANG Jianjun;LI Jing;MA Xuming;WAN Zhaofei;ZHU Bin;LIU Yaping;GUO Xiangqian;PAN Jiping;FAN Yan(Department of Orthopedics,the First People's Hospital of Lanzhou,Lanzhou,Gansu 730050,China;The Second Ward of Cardiology Department,Gansu Provincial Hospital,Lanzhou,Gansu 730000,China;Department of Cardiovascular Medicine,the Second Affiliated Hospital of Medical College,Xi'an Jiaotong University,Xi'an,Shaanxi 710004,China;Department of Emergency,Gansu Provincial Hospital,Lanzhou,Gansu 730000,China;Gansu University of Chinese Medicine,Lanzhou,Gansu 730000,China)

机构地区：[1]兰州市第一人民医院骨科,甘肃省兰州市730050 [2]甘肃省人民医院心内科二病区,甘肃省兰州市730000 [3]西安交通大学医学院第二附属医院心血管内科,陕西省西安市710061 [4]甘肃省人民医院急诊科,甘肃省兰州市730000 [5]甘肃中医药大学,甘肃省兰州市730000

出　　处：《中国动脉硬化杂志》2024年第8期654-662,共9页Chinese Journal of Arteriosclerosis

基　　金：甘肃省自然科学基金项目(20JR10RA406);甘肃省人民医院科研基金项目(23GSSYD-29)。

摘　　要：[目的]探讨脂肪间充质干细胞(ADMSC)外泌体(Exo)对心肌梗死(MI)后不良心室重塑的抑制作用和机制。[方法]观察心脏成纤维细胞经过氧化氢(H_(2)O_(2))处理后自噬和炎症表型的改变。MI大鼠经尾静脉注射等体积的生理盐水、ADMSC外泌体(MSC-Exo)、成纤维细胞外泌体(MEF-Exo),观察心脏成纤维细胞自噬相关16样蛋白1(ATG16L1)、自噬相关蛋白7(ATG7)和NOD样受体蛋白3(NLRP3)炎症小体的表达,炎症反应,心肌纤维化程度以及心功能。[结果]心脏成纤维细胞经H_(2)O_(2)处理后,自噬相关蛋白ATG16L1和ATG7表达显著降低(P<0.001),NLRP3表达显著升高(P<0.001),促炎细胞因子白细胞介素1β(IL-1β)和IL-18水平显著增加(P<0.001)。MI大鼠经MSC-Exo干预后,自噬相关蛋白ATG16L1和ATG7表达显著上调(P<0.001),NLRP3表达显著下调(P<0.001),血清IL-1β和IL-18水平显著降低(P<0.001),纤维化相关蛋白胶原蛋白Ⅰ和Ⅲ显著减少(P<0.001),心肌纤维化程度显著减轻(P<0.001),心功能明显改善(P<0.001)。[结论]脂肪MSC-Exo通过调控心脏成纤维细胞自噬和NLRP3炎症小体的平衡,发挥抑制MI后不良心室重塑的作用。Aim To investigate the inhibition role and mechanism of adipose derived mesenchymal stem cell(ADMSC)exosomes(Exo)on adverse ventricular remodeling after myocardial infarction(MI).Methods The changes of autophagy and inflammasomes phenotype of cardiac fibroblasts after H_(2)O_(2)treatment were observed.MI rats were injected with an equal volume of normal saline,adipose derived mesenchymal stem cell exosomes(MSC-Exo)or fibroblast exosomes(MEF-Exo)via a tail vein.The expression of autophagy related 16 like protein 1(ATG16L1),autophagy related protein 7(ATG7)and NOD-like receptor protein 3(NLRP3),inflammatory response,the degree of myocardial fibrosis,and the cardiac function were observed in different groups.Results After treatment with H_(2)O_(2)on cardiac fibroblasts,the expressions of ATG16L1 and ATG7 were significantly decreased(P<0.001),NLRP3 was significantly increased(P<0.001),and the levels of inflammatory cytokines interleukin-1β(IL-1β)and IL-18 were significantly elevated(P<0.001).After MI rats were intervened with MSC-Exo,the expressions of autophagy related proteins ATG16L1 and ATG7 were significantly up-regulated(P<0.001),NLRP3 was significantly down-regulated(P<0.001),serum IL-1βand IL-18 levels were significantly decreased(P<0.001),fibrosis-related proteins collagenⅠandⅢwere significantly reduced(P<0.001),myocardial fibrosis was significantly relieved(P<0.001),and cardiac function was significantly improved(P<0.001).Conclusion Adipose derived MSC-Exo play a role in inhibiting adverse ventricular remodeling after MI by regulating the balance of autophagy and NLRP3 inflammasomes.

关 键 词：脂肪间充质干细胞 外泌体 自噬相关16样蛋白1 自噬相关蛋白7 NLRP3炎症小体 心肌纤维化 心室重塑 心肌梗死 

分 类 号：R543.3[医药卫生—心血管疾病] R363[医药卫生—内科学]