Abstract:

The purpose of this study was to determine the optimal concentration of sodium butyrate in regulating the expression of cytokines and tight junction proteins in human intestinal epithelial cells (FH_S 74 int cells) by cell experiments, and to further explore the effects of sodium butyrate on ileum development, inflammatory factors and physical barrier function in young rats. In cell experiments, FH_S 74 int cells were selected to explore the effects of different concentrations of sodium butyrate on cell viability, expression levels of inflammatory factors and tight junction protein. In animal experiment, 32 newborn C57BL/6J mice were randomly divided into 4 groups, each with 8 mice, namely the control group (0.9% normal saline), SB20 group (20 mg·kg^-1 BW sodium butyrate), SB350 group (350 mg·kg^-1 BW sodium butyrate), and SB1000 group (1 000 mg·kg^-1 BW sodium butyrate). After continuous administration for 30 days, body weight, blood routine, ileal histological morphology, ileal cytokine and tight junction protein gene expression levels of mice were detected. In vitro, 12.5 and 25 mmol·L^-1 sodium butyrate increased the gene and protein expression of occludin in cells, and 25 mmol·L^-1 sodium butyrate significantly increased the gene expression of GPR109A and the gene and protein expression of ZO-1. In animal experiment, there were no significant differences in body weight and blood routine indexes among the groups of mice. Through ileal pathology, it was found that 350 mg·kg^-1 BW sodium butyrate significantly increased the ileal villus height but reduce the crypt depth of young mice (P < 0.05). At the same time, it increased the relative mRNA expression of ileal anti-inflammatory factors IL-4 and IL-10, while decreasing the relative mRNA expression of pro-inflammatory factor IL-18. 1 000 mg·kg^-1 BW sodium butyrate significantly increased the ratio of villus height to crypt depth of ileum (P < 0.05), decreased the crpyt depth and the relative mRNA expression of pro-inflammatory factor TNF-α. In conclusion, 25 mmol·L^-1 sodium butyrate can promote the gene expression of occludin, ZO-1, and GPR109A in FH_S 74 int cells, maintaining barrier function. Sodium butyrate at 350 mg·kg^-1 BW can promote the development of the ileum morphological structure of mice, increase villus height, reduce crypt depth, and simultaneously regulate the gene expression of intestinal inflammatory factors and tight junction proteins.

Key words: sodium butyrate, FH_S 74 int cells, intestinal barrier, tight junction protein