期刊
INTERNATIONAL IMMUNOPHARMACOLOGY
卷 88, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.intimp.2020.106961
关键词
Resolvin D1; Non-alcoholic steatohepatitis; Inflammation; Oxidative stress
资金
- National Natural Science Foundation of China [81670515, 81800519]
Aims: Resolvin D1 (RvD1), a potent endogenous lipid mediator converted from docosahexaenoic acid (DHA), has exert anti-inflammatory and antioxidant effects in many preclinical disease models, but its potential role in non-alcoholic steatohepatitis (NASH) remains elusive. This study was performed to investigate the protective effects and mechanisms of RvD1 in NASH. Main methods: In vivo, male C57BL/6 mice were fed an MCD diet for 4 weeks to induce NASH. RvD1 was added in the last 2 weeks of the feeding period. In vitro, lipopolysaccharide (LPS)-activated RAW264.7 macrophages were pretreated with increasing concentrations of RvD1. Serum liver functional markers and hepatic oxidative stress indicators were measured biochemically. Mouse liver tissue sections were stained with hematoxylin-eosin, oil red O, and Masson's trichrome to assess the severity of steatohepatitis, steatosis and fibrosis. The qRT-PCR, immunohistochemistry and Western blotting assays were applied to analyse mechanisms underlying RvD1 protection in NASH. Key findings: In vivo, RvD1 significantly attenuates steatohepatitis in MCD diet-fed mice by modulating key events, including steatosis, inflammation, oxidative stress and fibrosis in the progression of NASH. In vitro, RvD1 also represses LPS-induced inflammation in RAW264.7 cells. These effects may be mainly attributed to RvD1 markedly suppressing excessive inflammatory responses via the inhibition of the TLR4-MyD88-mediated NF-kappa B and MAPK signalling pathways as well as enhancing antioxidation capacity via the activation of the Nrf2 pathway. Significance: These results demonstrate that RvD1 is a promising hepatoprotective agent for the therapy of NASH.
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