Hydrogen sulfide ameliorates rat myocardial fibrosis induced by thyroxine through PI3K/AKT signaling pathway

This study aims to investigate the role and regulatory mechanism of the Hydrogen sulfide (H₂S) in amelioration of rat myocardial fibrosis induced by thyroxine through interfering the autophagy via regulating the activity of PI3K/AKT1 signaling pathway and the expression of relative miRNA. 40 adult male SD rats were randomly divided into 4 groups (n = 10): the control group, the thyroxine model group (TH group), the model group with H₂S intervention (TH + H₂S group) and the normal group with H₂S intervention (H₂S group). Pathological changes were observed via H&E staining and Masson staining, Expressions of MMPs/TIMPs, PI3K/AKT, autophagy-related proteins in myocardial tissues were detected via Western blotting, and the expressions of miR-21, miR-34a, miR-214 and miR-221 were detected via RT-qPCR. Compared with the control group, in the TH group, myocardial fibrosis was more significant, the expressions of proteins in PI3K/AKT and autophagy-related proteins were significantly decreased, as well as the expression of miR-221; while the expressions of miR-21, miR-34a and miR-214 were significantly elevated. By contrast, all above-mentioned changes were obviously reversed with H₂S treatment, which demonstrated the positive function of H₂S in amelioration of rat myocardial fibrosis induced by thyroxine. The mechanism of such amelioration may be correlated with autophagy activated by the upregulation of expression of PI3K/AKT signaling pathway and downregulation of expressions of miR-21, miR-34a and miR-214.