Abstract
The present study aimed to determine the role and regulatory mechanism of hydrogen sulfide (H2S) in the amelioration of doxorubicin‑induced myocardial fibrosis in rats. It is hypothesized that the PI3K/AKT/mTOR signaling pathway is regulated to inhibit endoplasmic reticulum stress (ERS) and autophagy to reduce myocardial fibrosis. A total of 40 adult male Sprague Dawley rats were randomly divided into 4 groups (n=10/group). The 4 groups included the normal control group (control group), model group [doxorubicin (Dox) group], H2S intervention model group (H2S+Dox group) and H2S control group (H2S group). The model used in the present study was constructed by administering intraperitoneal injections of doxorubicin (3.0 mg/kg every other day; total of 6 injections). In addition, the intervention factor, NaHS and the donor of H2S, was also administered by intraperitoneal injection (56 µmol/kg/day), which lasted a month. Pathological changes in the rats were observed using Masson staining and transmission electron microscopy, while the protein expression levels of MMPs/TIMPs, transforming growth factor‑β1, cystathionine lyase and PI3K/AKT/mTOR, which are autophagy‑related and ERS‑related proteins were detected in myocardial tissues using western blot analysis. The gene expression levels of collagen type I α‑2 chain and collagen type III α‑1 chain were detected using reverse transcription‑quantitative PCR and the quantification of myocardial H2S content was performed using ELISA. In the Dox group compared with that in the control group, myocardial fibers were significantly disordered, while the protein expression levels of ERS‑related and autophagy‑related proteins were increased markedly, and the expression levels of PI3K/AKT/mTOR proteins were reduced markedly. The aforementioned changes were markedly reversed following H2S intervention, which indicated that H2S exerts a positive protective effect on doxorubicin‑induced myocardial fibrosis. The protective mechanism of H2S intervention in myocardial fibrosis is hypothesized to be associated with the inhibition of overactivation of the ER and that of autophagy via upregulation of the PI3K/AKT/mTOR pathway.