Journal of Jilin University Medicine Edition ›› 2015, Vol. 41 ›› Issue (04): 751-755.doi: 10.13481/j.1671-587x.20150416

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Effect of LPS-TLR4 pathway in hepatic fibrogenesis of rats with chronic alcohol intake

YANG Kun1, TIAN Zhenzhen2, WANG Shuhua3, XIU Ming1, GUO Xiangling1, QI Lina1, LI Min1, SUN Li1, GAO Runping1   

  1. 1. Department of Hepatic-Biliary-Pancreatic Medicine, First Hospital, Jilin University, Changchun 130021, China;
    2. Department of Geratology, Affiliated Hospital, Jiangsu University, Zhenjiang 21200, China;
    3. Department of Gastroenterol Surgery, First Hospital, Jilin University, Changchun 130021, China
  • Received:2014-11-17 Published:2015-08-01

Abstract:

Objective To determine the levels of lipopolysaccharide (LPS) in portal vein blood from the chronic intake rats,and to explore the mechanism and significance of LPS-Toll-like receptor 4 (TLR4) pathway in hepatic fibrogenesis in the rat models of chronic alcohol intake. Methods Twenty-four male Sprague-Dawley rats were randomly divided into alcohol group and control group,and the rats were fed with isocaloric Lieber-Decarli alcohol liquid diets and control diets for 10 weeks.The histological characteristics of liver tissue of the rats were evaluated by HE staining and Masson Trichrome staining.The plasma LPS levels in portal veins of the rats were determined by spectrophotometric method. The fibroblast specific protein 1(FSP-1) and vimentin were determined for identification of hepatic stellate cells (HSCs) by immunohistochemistry.The TLR4 mRNA expression levels in rat liver tissue were examined by in situ hybridization method.Computer image analysis was performed to measure the integrated optimal density (IA) of FSP-1-positive HSCs or TLR4 mRNA-positive cells,respectively.The expression levels of interleukin 1(IL-1),interleukin 6(IL-6),tumor necrosis factor α(TNF-α) and transforming growth factor beta 1(TGF-β1) mRNA in liver tissue were detected by RT-PCR. Results Compared with control group, the liver tissue of the rats in alcohol group showed a mild perisinusoidal and periportal fibrosis;the expression level of TLR4 mRNA and the number of FSP-1-positive HSCs were increased at the end of 10 weeks (P<0.05).At the end of 10 weeks,the plasma LPS level in portal veins of the rats in alcohol group was significantly higher than that in control group (P<0.01).Compared with control group,the expression levels of IL-1,IL-6,TNF-α and TGF-β1 mRNA in liver tissue of the rats in alcohol group were increased significantly(P<0.01).Bivariate correlation analysis showed that there was a positive correlation between the expression intensity of TLR4 mRNA in liver tissue and the levels of portal vein plasma LPS of the rats in alcohol group (r=0.856,P<0.05). Conclusion The activation of TLR4 pathway triggered by chronic intake plays an important role in the rat hepatic fibrogensis through up-regulation of profibrogenic and proinflammatory cytokine release.

Key words: lipopolysaccharide, Toll-like receptor 4, hepatic stellate cells, hepatic fibrosis, alcohol

CLC Number: 

  • R575