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ISSN 1001-5256
CN 22-1108/R
Issue 8
Aug.  2017
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Effect of trefoil factor 3 on intestinal mucous barrier in rats with nonalcoholic steatohepatitis

DOI: 10.3969/j.issn.1001-5256.2017.08.029
  • Received Date: 2017-02-22
  • Published Date: 2017-08-20
  • Objective To investigate the change in intestinal mucous barrier in rats with nonalcoholic steatohepatitis ( NASH) , the effect of trefoil factor 3 ( TFF3) on intestinal mucous barrier in NASH rats, and the therapeutic effect of TFF3 on NASH. Methods A total of 60 clean male Sprague-Dawley rats were randomly divided into normal group, model group, and treatment group, with 20 rats in each group.The rats in the normal group were given normal diet, and those in the model group and the treatment group were given high-fat diet to induce NASH. The rats in the treatment group were given intraperitoneal injection of rh TFF3 at a dose of 1 ml·kg-1·d-1 ( a concentration of 0. 1 mg/ml) , and those in the normal group and the model group were given normal saline at a dose of 1 ml·kg-1·d-1; the course of treatment was 3 weeks for all groups. At the end of week 15, fluorescein isothiocyanate-labeled dextran was given by gavage to evaluate intestinal permeability, and after the rats were sacrificed, serum levels of aspartate aminotransferase ( AST) , alanine aminotransferase ( ALT) , total cholesterol ( TC) , triglyceride ( TG) , and endotoxin ( ET) and diamine oxidase ( DAO) activity were measured. HE staining was performed to observe the histopathological changes of the liver and the terminal ileum, PAS staining was performed to observe and count the goblet cells of the terminal ileum, immunohistochemistry was used to measure the expression of the tight junction protein Occludin and TFF3 in the terminal ileum, and quantitative real-time PCR was used to measure the mRNA transcription level of TFF3. A one-way analysis of variance was used for comparison between multiple groups, and the least significant difference t-test was used for further comparison between any two groups. Results The model group had significant increases in serum levels of AST, ALT, TC, TG, and ET and DAO activity, and the treatment group had significant reductions compared with the model group ( all P < 0. 01) . The model group had a significant increase in NAFLD activity score compared with the normal group ( P < 0. 01) , and the treatment group had significant improvement in liver inflammation and a significant reduction in NAFLD activity score compared with the model group ( P < 0. 01) . The model group had cell necrosis, damage of the intestinal villi, and a significant reduction in goblet cells in the terminal ileum under a light microscope; in the treatment group, damage of the intestinal villi was repaired and there was an increase in goblet cells. The model group had a significant increase in intestinal permeability compared with the normal group, and the treatment group had a significant reduction compared with the model group ( both P < 0. 01) . The model group had a significant reduction in the expression of Occludin and TFF3, and the treatment group had a significant increase compared with the model group ( all P < 0. 01) . The model group had a downregulated TFF3 mRNA transcription level in the terminal ileum compared with the normal group, and the treatment group had an upregulated level compared with the model group ( both P < 0. 01) . Conclusion NASH rats have damaged goblet cells and mucous barrier dysfunction. TFF3 can repair the damaged terminal ileum, promote the regeneration of goblet cells and mucus secretion, restore intestinal barrier function, reduce intestinal permeability, and thus exert its therapeutic effect on NASH.

     

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