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Hydrogen sulfide ameliorates doxorubicin‑induced myocardial fibrosis in rats via the PI3K/AKT/mTOR pathway

  • Authors:
    • Liangui Nie
    • Maojun Liu
    • Jian Chen
    • Qian Wu
    • Yaling Li
    • Jiali Yi
    • Xia Zheng
    • Jingjing Zhang
    • Chun Chu
    • Jun Yang
  • View Affiliations / Copyright

    Affiliations: Department of Cardiology, The First Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China, Department of Pharmacy, The Second Affiliated Hospital of University of South China, Hengyang, Hunan 421001, P.R. China
    Copyright: © Nie et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 299
    |
    Published online on: February 24, 2021
       https://doi.org/10.3892/mmr.2021.11938
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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.
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Copy and paste a formatted citation
Spandidos Publications style
Nie L, Liu M, Chen J, Wu Q, Li Y, Yi J, Zheng X, Zhang J, Chu C, Yang J, Yang J, et al: Hydrogen sulfide ameliorates doxorubicin‑induced myocardial fibrosis in rats via the PI3K/AKT/mTOR pathway. Mol Med Rep 23: 299, 2021.
APA
Nie, L., Liu, M., Chen, J., Wu, Q., Li, Y., Yi, J. ... Yang, J. (2021). Hydrogen sulfide ameliorates doxorubicin‑induced myocardial fibrosis in rats via the PI3K/AKT/mTOR pathway. Molecular Medicine Reports, 23, 299. https://doi.org/10.3892/mmr.2021.11938
MLA
Nie, L., Liu, M., Chen, J., Wu, Q., Li, Y., Yi, J., Zheng, X., Zhang, J., Chu, C., Yang, J."Hydrogen sulfide ameliorates doxorubicin‑induced myocardial fibrosis in rats via the PI3K/AKT/mTOR pathway". Molecular Medicine Reports 23.4 (2021): 299.
Chicago
Nie, L., Liu, M., Chen, J., Wu, Q., Li, Y., Yi, J., Zheng, X., Zhang, J., Chu, C., Yang, J."Hydrogen sulfide ameliorates doxorubicin‑induced myocardial fibrosis in rats via the PI3K/AKT/mTOR pathway". Molecular Medicine Reports 23, no. 4 (2021): 299. https://doi.org/10.3892/mmr.2021.11938
Copy and paste a formatted citation
x
Spandidos Publications style
Nie L, Liu M, Chen J, Wu Q, Li Y, Yi J, Zheng X, Zhang J, Chu C, Yang J, Yang J, et al: Hydrogen sulfide ameliorates doxorubicin‑induced myocardial fibrosis in rats via the PI3K/AKT/mTOR pathway. Mol Med Rep 23: 299, 2021.
APA
Nie, L., Liu, M., Chen, J., Wu, Q., Li, Y., Yi, J. ... Yang, J. (2021). Hydrogen sulfide ameliorates doxorubicin‑induced myocardial fibrosis in rats via the PI3K/AKT/mTOR pathway. Molecular Medicine Reports, 23, 299. https://doi.org/10.3892/mmr.2021.11938
MLA
Nie, L., Liu, M., Chen, J., Wu, Q., Li, Y., Yi, J., Zheng, X., Zhang, J., Chu, C., Yang, J."Hydrogen sulfide ameliorates doxorubicin‑induced myocardial fibrosis in rats via the PI3K/AKT/mTOR pathway". Molecular Medicine Reports 23.4 (2021): 299.
Chicago
Nie, L., Liu, M., Chen, J., Wu, Q., Li, Y., Yi, J., Zheng, X., Zhang, J., Chu, C., Yang, J."Hydrogen sulfide ameliorates doxorubicin‑induced myocardial fibrosis in rats via the PI3K/AKT/mTOR pathway". Molecular Medicine Reports 23, no. 4 (2021): 299. https://doi.org/10.3892/mmr.2021.11938
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