Intestinal Trefoil Factor 3 Alleviates the Intestinal Barrier Function Through Reducing the Expression of TLR4 in Rats with Nonalcoholic Steatohepatitis.

BACKGROUND

Previous studies have reported that nonalcoholic steatohepatitis (NASH) is relevant to intestinal mucosal barrier dysfunction.

AIM OF THE STUDY

To investigate the effects of intestinal trefoil factor 3 (TFF3) on intestinal barrier function and endotoxin/toll-like receptor 4(TLR4) expression in NASH rats.

METHODS

Sixty NASH rats were divided into control, NASH and NASH-TFF3 treated group. Intestinal permeability, serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), endotoxin (ET), diamine oxidase (DAO) and liver index were examined. HE and PAS staining were performed to observe the histopathology of liver and terminal ileum. Expression of TFF3 and occludin were detected by immunohistochemical staining. mRNA and protein expression of TLR4, nuclear factor-κB (NF-κB), Mucin-2(Muc2) were detected by RT-qPCR and Western Blot. Interleukin (IL) -1β and IL-10 levels in the ileum were measured by ELISA.

RESULTS

In NASH group, levels of AST, ALT, ET, DAO, NAS, liver index and intestinal permeability were higher while occludin expressions were lower than control and NASH-TFF3 treated groups (p <0.05). Histopathology examination showed pathological damages of liver and ileum were alleviated in NASH-TFF3 treated group. NASH-TFF3 treated group had decreased expression levels of TLR4 and NF-κB and increased expression levels of Muc2 than NASH group. Besides, NASH group showed increased IL-1β and IL-10 levels compared with control group. NASH-TFF3 treated group showed decreased IL-1β level however increased IL-10 level compared with NASH group.

CONCLUSION

Recombinant human TFF3 (rhTFF3) can reduce the expression of TLR4, reduce intestinal permeability, alleviate liver damage and thus may play a therapeutic role in the treatment of NASH rats.