Hydrogen sulfide ameliorates abdominal aorta coarctation-induced myocardial fibrosis by inhibiting pyroptosis through regulating eukaryotic translation initiation factor 2α phosphorylation and activating PI3K/AKT1 pathway

This study aimed to assess the effects of exogenous hydrogen sulfide (H(2)S) on abdominal aorta coarctation (AAC) induced myocardial fibrosis (MF) and autophagy in rats. Forty-four Sprague–Dawley rats were randomly divided into control group, AAC group, AAC + H(2)S group, and H(2)S control group. After a model of rats with AAC was built surgically, AAC + H(2)S group and H(2)S group were injected intraperitoneally with H(2)S (100 μmol/kg) daily. The rats in the control group and the AAC group were injected with the same amount of PBS. We observed that H(2)S can improve left ventricular function and the deposition of myocardial collagen fibers, inhibit pyroptosis, down-regulate the expression of P-eif2α in myocardial tissue, and inhibit cell autophagy by activating the phosphatidylinositol 3-kinase (PI3K)/AKT1 signaling pathway (p < 0.05). In addition, angiotensin II (1 μM) H9c2 cardiomyocytes were injured in vitro experiments, and it was also observed that pyroptosis was inhibited after H(2)S (400 μmol/kg) intervention, the expression of P-eif2α in cardiomyocytes was significantly down-regulated, and the PI3K/AKT1 signaling pathway was activated at the same time. Therefore, increasing the expression of P-eif2α reverses the activation of the PI3K/AKT1 signaling pathway by H(2)S. In conclusion, these findings suggest that exogenous H(2)S can ameliorate MF in rats with AAC by inhibiting pyroptosis, and the mechanism may be associated with inhibiting the phosphorylation of eif2α and activating the PI3K/AKT1 signaling pathway to inhibit excessive cell autophagy.