Protective effects of aryl hydrocarbon receptor activation on intestinal barrier damage in a mouse model of total parenteral nutrition

Abstract

Objective To investigate the protective effects of aryl hydrocarbon receptor (AhR) activation of 6-formylindolo [3, 2-B] carbazole (FICZ) on intestinal barrier damage and its potential mechanism in a mouse model of total parenteral nutrition (TPN). Methods TPN model was established in 18 mice with fluid infusion via external jugular vein, and then the mice randomly divided into control, TPN and TPN+FICZ (1 μg/d) groups. The mice of the TPN group and the TPN+FICZ group were infused with TPN solution and FICZ, those in the control group were treated with same amount of normal saline, and the mice of control group were allowed to eat freely. Their body weight were observed before and in 7 d after catheterization, and peripheral blood sample were harvested to detect intestinal barrier markers. All mice were sacrificed on day 7, and the terminal tissue of ileum was retained to detect protein and RNA expression of relevant molecules and observe the morphological changes of intestinal mucosa. Results After 7 d, when compared with the mice of the control group, the mice in the TPN group showed significantly decreased body weight, shorter length of small intestine (P < 0.05), obvious mucosal damages in the intestine, higher Chiu score, increased serum levels of FITC and iFABP (intestinal barrier function indicators), and enhanced expression levels of TNF-α and IL-1β (P < 0.05), but obviously decreased level of CYP1A1 (an indicator of intestinal AhR activation), and the levels of intestinal barrier tight junction proteins Zo-1 and Occludin and anti-inflammatory factor IL-10 in intestinal tissue (P < 0.05). While, FICZ intervention attenuated above changes in body weight and intestinal length (P < 0.05), improved mucosal damage, reduced Chiu score (P < 0.05), declined serum levels of FITC and iFABP and the levels of TNF-α and IL-1β in intestinal tissue (P < 0.05), and up-regulated the expression levels of CYP1A1, Zo-1, Occludin and IL-10 (P < 0.05). Conclusion FICZ attenuates TPN-induced intestinal barrier damage in mice through AhR activation to relieve inflammation of intestinal mucosa and regulate expression of tight junction proteins.

Keywords

• total parenteral nutrition
• aryl hydrocarbon receptor
• intestinal barrier