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.

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 H2O2 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 H2O2 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-1β and IL-18 levels were significantly decreased (P<0. 001), fibrosis-related proteins collagen Ⅰ and Ⅲ were 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. [ABSTRACT FROM AUTHOR]