Treatment of experimental non‑alcoholic steatohepatitis by targeting α7 nicotinic acetylcholine receptor‑mediated inflammatory responses in mice

Zhou,Zhou; Liu,Ying‑Chao; Chen,Xiao‑Mei; Li,Fu‑Qiang; Tong,Xiao‑Juan; Ding,Yue‑Ping; Tang,Cui‑Lan

doi:10.3892/mmr.2015.4318

Treatment of experimental non‑alcoholic steatohepatitis by targeting α7 nicotinic acetylcholine receptor‑mediated inflammatory responses in mice

Authors:
- Zhou Zhou
- Ying‑Chao Liu
- Xiao‑Mei Chen
- Fu‑Qiang Li
- Xiao‑Juan Tong
- Yue‑Ping Ding
- Cui‑Lan Tang
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Affiliations: Department of Anesthesiology, The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310053, P.R. China, Department of Digestive Diseases, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310005, P.R. China, Department of Infectious Disease, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310005, P.R. China, Department of Intensive Care Unit, The Second Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310005, P.R. China
Published online on: September 10, 2015 https://doi.org/10.3892/mmr.2015.4318
Pages: 6925-6931

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Abstract

Non‑alcoholic fatty liver disease (NAFLD) is one of the most common types of liver disease, affecting up to 30% of the general population worldwide. Non‑alcoholic steatohepatitis (NASH) is a severe form of NAFLD without any effective therapies available. The present study showed that activation of α7‑nicotinic acetylcholine receptor (α7 nAChR) may be a novel potential strategy for NASH therapy. Treatment with the α7 nAChR agonist nicotine for three weeks obviously attenuated hepatic steatosis in a high-fat diet‑induced mouse model of NASH. Investigation of the underlying mechanism showed that nicotine reduced the secretion of the pro‑inflammatory cytokines tumor necrosis factor α and interleukin 6 in vitro and in vivo. Inflammation is an integral part of NASH and is the most prevalent form of hepatic pathology found in the general population; therefore, the effect of α7 nAChR activation against NASH may be ascribed to its anti‑inflammatory effects. In addition, the present study showed that nicotine‑stimulated α7 nAChR activation led to a significant downregulation of nuclear factor kappa B (NK‑κB) and extracellular signal-regulated kinase (ERK). It therefore appeared that activation of α7 nAChR suppressed the production of pro‑inflammatory cytokines through NK‑κB and ERK pathways. In conclusion, the present study indicated that targeting α7 nAChR may represent a novel treatment strategy for NASH.

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