The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Hemin attenuates bleomycin-induced lung fibrosis in mice by regulating the TGF-β1/MAPK and AMPK/SIRT1/PGC-1α/HO-1/ NF-κB pathways

  • Wei Hao (Department of Functional Experimental Training Center) ;
  • Ting-ting Yu (Department of Functional Experimental Training Center) ;
  • Wei Li (Department of Pathophysiology, Basic Medical College, Wannan Medical College) ;
  • Guo-guang Wang (Department of Pathophysiology, Basic Medical College, Wannan Medical College) ;
  • Hui-xian Hu (Department of Medical Imageology, Wannan Medical College) ;
  • Ping-ping Zhou (Department of Physiology, Basic Medical College, Wannan Medical College)
  • Received : 2024.03.29
  • Accepted : 2024.04.26
  • Published : 2024.11.01
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Abstract

The objective of this study was to investigate the protective effect and potential mechanism of action of hemin on bleomycin-induced pulmonary fibrosis in mice. Male C57BL/6 mice were randomly divided into control, bleomycin and bleomycin + hemin groups. Mice in the bleomycin and bleomycin + hemin groups were injected intratracheally with bleomycin to establish the pulmonary fibrosis model. The bleomycin + hemin group mice were injected intraperitoneally with hemin starting 7 days before modeling until the end of Day 21 after modeling. Pathological changes in lung tissue were assessed by HE and Masson staining. Malondialdehyde (MDA), superoxide dismutase (SOD) and catalase (CAT) levels were determined in lung tissue. Immunohistochemistry was performed to assess the expression of α-SMA and collagen I. The serum levels of IL-6 and TNF-α were measured via ELISA. Western blotting was used to determine the expression of TGF-β1, SIRT1, PGC-1α and HO-1 and the phosphorylation levels of p38, ERK1/2, JNK, AMPK and NF-κB p65 in lung tissue. Hemin significantly reduced lung indices, increased terminal body weight. It also significantly increased SOD and CAT activities; decreased MDA, IL-6 and TNF-α levels; reduced the levels of α-SMA and collagen I-positive cells; upregulated SIRT1, PGC-1α and HO-1 expression; promoted AMPK phosphorylation; and downregulated TGF-β1 expression and p38, ERK1/2, JNK and NF-κB p65 phosphorylation. Hemin might attenuate oxidative damage and inflammatory responses and reduces extracellular matrix deposition by regulating the expression and phosphorylation of proteins associated with the TGF-β1/MAPK and AMPK/SIRT1/PGC-1α/HO-1/NF-κB pathways, thereby alleviating bleomycin-induced pulmonary fibrosis.

Keywords

Acknowledgement

This work was supported by the Key Project of Scientific Research in Colleges and Universities of Anhui Province (Natural Sciences) in 2023 (2023AH051755) and the Key Project of Scientific Research in Wannan Medical College (Natural Sciences) in 2023 (WK2023ZZD06).

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