Protective Effect Of Sodium Butyrate On Intestinal Mucosal Barrier Injury And Uric Acid Reduction In Hyperuricemia Mouse Model

Objective:To investigate the protective effects of potassium oxyzinate combined with high yeast feed on the integrity of intestinal mucosal barrier in hyperuricemia mice and sodium butyrate on intestinal mucosal barrier damage and serum uric acid reduction in hyperuricemia mice.Methods:1.In vitro experiments:Different concentrations of uric acid and sodium butyrate were used to intervene in LS174t cell lines and Cac2 cell lines.Western blot and RT-q PCR methods were used to detect the expression levels of MUC2 protein and m RNA in LS174t cell lines,as well as the expression levels of ZO-1,Occludin protein and m RNA in Cac2 cell lines.2.Animal experiment:C57BL/6 mice were randomly divided into control group,model group,and sodium butyrate group.The mice in the control group were fed ordinary feed,while the mice in the model group and sodium butyrate group were administered 200mg.Kg^-1.d^-1（suspended in 0.5%CMC-Na）intraperitoneally,and were fed high yeast feed.The mice in the sodium butyrate group were administered potassium oxyzinate intraperitoneally,while sodium butyrate was administered by gavage.On the 21st day,the levels of uric acid（uric acid）and fecal short chain fatty acids（SCFAs）in mice were detected and the mice were killed.Western blot and RT-q PCR were used to detect the expression of MUC2,ZO-1,and Occludin proteins and m RNA in intestinal tissue,and enzyme linked immunosorbent assay（ELISA）was used to detect the levels of inflammatory factors IL-6 and TNF-αin intestinal tissue,Hematoxylin-eosin（HE）staining and Alcian blue-periodate-Scheff（AB-PAS）staining were used to evaluate the pathological changes and intestinal mucus secretion.Results:1.In vitro experiments showed that uric acid down-regulated the expression of protein and m RNA of ZO-1,Occludin and MUC2 in Ls174t and Caco2 cell lines（P<0.05）.2.Low-concentration sodium butyrate up-regulated the expression of ZO-1,Occludin and MUC2 proteins in LS174t and Caco2 cell lines（P<0.05）.3.Low concentration of sodium butyrate can up-regulate the expression of ZO-1,Occludin and MUC2 protein and m RNA in Ls174t and Caco2 cell lines due to high uric acid（P<0.05）.4.The serum uric acid level in hyperuricemia mice model group（353.18±57.32μmol/L）was significantly higher than that in control group（110.35±18.33μmol/L）（P<0.01）.The fecal SCFAs content in hyperuricemia mice model group（29.75±9.24 ug/g）was significantly lower than that in control group（217.90±78.15 ug/g）（P<0.05）.The serum uric acid level in the sodium butyrate group（276.82±65.73μmol/L）was significantly lower than that in the model group（353.18±57.32μmol/L）（P<0.05）.5.The expression of MUC2,ZO-1 and Occludin protein and m RNA in the intestinal tissue of the model group decreased（P<0.05）.The levels of inflammatory factors IL-6 and TNF-αin the intestinal tissue of the model group（801.39±113.88 pg/ml,173.69±65.83 pg/ml）were significantly higher than those in the control group（309.84±40.04 pg/ml,57.99±16.53 pg/ml）（P<0.001）,suggesting that the hyperuricemia mouse model has intestinal barrier damage.6.The expression of MUC2,ZO-1 and Occludin protein and m RNA in intestinal tissue of mice in sodium butyrate group was significantly higher than that in model group（P<0.05）.The levels of IL-6 and TNF-α（310.55±45.92 pg/ml,55.97±9.20 pg/ml）were lower than those in model group（801.39±113.88 pg/ml,173.69±65.83 pg/ml）（P<0.001）.7.The results of HE staining and AB-PAS staining also support the protective effect of sodium butyrate on the intestinal barrier in mice with hyperuricemia.8.Western Blot,immunohistochemistry and RT-q PCR results showed that the expression of ABCG2protein and m RNA in the intestinal tissue of the model group was down-regulated（P<0.05）,and the expression of ABCG2 protein in the sodium butyrate group was significantly up-regulated compared with the model group（P<0.05）.Conclusion:1.There is intestinal barrier damage in the hyperuricemia mouse model induced by potassium oxyzinate combined with high yeast feed.2.Sodium butyrate can protect the intestinal barrier of hyperuricemia model mice and reduce the serum uric acid level.3.Sodium butyrate can reduce the level of serum uric acid in hyperuricemia model mice.4.Sodium butyrate may play a role in lowering uric acid by up-regulating the expression of intestinal uric acid transporter ABCG2 protein.