• Khalil Hajiasgharzadeh, Seyed Mohammad Tavangar, Mohammad Javan, Ahmad R Dehpour, and Ali R Mani.
• Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
• Auton Neurosci. 2014 Oct 1; 185: 67-75.

AbstractRecent studies have shown that vagus nerve activation inhibits cytokine production in a variety of non-neural cells though activation of α7 nicotinic acetylcholine receptor (α7nAChR). Since chronic inflammation plays a pivotal role in liver fibrosis, this study was designed to investigate the role of hepatic vagus nerve in the progression of hepatic fibrosis in rats. Cirrhosis was induced by chronic ligation of the bile duct. Hepatic hydroxyproline level, portal pressure, serum transaminase level, hepatic TIMP-1 (tissue inhibitor of metalloproteinase-1) and MCP-1 (monocyte chemoattractant peptide-1) expression were measured in order to assess the progression of liver cirrhosis. α7nAChR expression was assessed using RT-PCR as well as immunostaining. RT-PCR analysis of the liver showed that α7nAChR mRNA is expressed in rat liver. Immunostaining study demonstrated that hepatic α7nAChR is mainly expressed in the hepatocytes of cirrhotic liver with minimum α7nAChR expression in biliary epithelium or myofibroblasts. Bile duct ligation was associated with portal hypertension, increased hepatic hydroxyproline level as well as TIMP-1 and MCP-1 expression in the liver. However neither selective hepatic vagotomy nor methyllycaconitine (an α7nAChR antagonist) could significantly affect development of portal hypertension or hepatic fibrosis in rats. Selective hepatic vagotomy could only attenuate serum aspartate aminotransferase level in bile duct ligated rats but did not have a significant effect on hepatic inflammation as assessed by MCP-1 mRNA expression. Our study provides evidence against a crucial role for the hepatic vagus nerve as an intrinsic protective mechanism in modulation of hepatic fibrosis in a rat model of biliary cirrhosis. Copyright © 2014 Elsevier B.V. All rights reserved.

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