Protective Effect Of Seleno-aminoligosaccharide On Colitis Induced By Dextran Sodium Sulfate In Mice

As the main source of dietary selenium supplements,selenium-enriched foods and health products have become one of the hotspots in the research and development of functional nutritional products in my country.In this study,as an organic selenium preparation,Seleno-aminooligosaccharide(SOA)was synthesized and used to explore protect effect on dextran sulfate sodium(DSS)-induced colitis of mice.The research includes the following four parts:(1)The effect of SOA on the colonic epithelial barrier of DSS-induced colitis mice.In animal experiments,ICR mice were randomly divided into four groups: control group(CON),model group(DSS),high-dose SOA group(SOA,600 mg/kg),and low-dose SOA group(d-SOA,300 mg/kg).SOA significantly improved colitis evidenced by body weight,organ index and disease active index of mice.HE stains of paraffin sections and electron microscope images showed that SOA restored number of goblet cells,tight junctions,intestinal microvilli and mucosal morphology in colitis mice,and reduced the damage to the epithelial surface of colonic mucosa.The results of enzyme-linked immunosorbent assay showed that SOA significantly reduced serum DAO level and liver LPS level in colitis mice,increased GSH-PX,SOD levels of serum and colon,and decreased TNF-α,IL-6 levels of serum and colon.Quantitative Real PCR results showed that SOA significantly reduced the m RNA expression of TNF-α and IL-6,increased the m RNA expression of occludin and ZO-1 in the colon of colitis mice.Our data indicated that SOA reduced the intestinal permeability,maintained the integrity of the intestinal epithelium,reduced oxidative stress and inflammation,and enhanced the intestinal epithelial barrier function of colitis mice.The protective effect of 600 mg/kg SOA on the colonic epithelial barrier of colitis mice was significantly stronger than that of 300 mg/kg SOA.(2)The effect of SOA on the structure of colonic mucin 2 glycan chains to DSS-induced colitis mice.LC-MS results showed that DSS induced a decrease in the abundance of mucin 2 glycan structures(Core 1,Core 3,Core 4 glycans and acidic glycans)and shortening of mucin 2 glycan chain in colon of mice.600 mg/kg SOA increased the relative abundance of MUC2 glycan structure and extended glycan chain length,including Core 3,Core 4 glycans and sulfated glycans.Our data indicated that SOA restored mucus barrier function by improving the glycan chain structures of colonic mucin 2 of colitis mice.(3)The effect of SOA on the intestinal bacteria in DSS-induced colitis mice.16 S r DNA sequence results showed that 600 mg/kg SOA significantly increased the abundance and diversity of the colonic bacteria in colitis mice,down-regulated the relative abundance of mucus utilizing bacteria(Lactobacillus),and up-regulated the relative abundance of beneficial bacteria(Mucispirillum,Erysipelotrichi).Short chain fat acid(SCFA)-producing bacteria were up-regulated by 600 mg/kg SOA,including Candidatus Soleaferrea,Ruminiclostridium 9 and Negativibacillus.Our data showed that SOA restored the intestinal microecology by regulating the imbalance of colonic bacteria in colitis mice.(4)The effect of SOA on colonic metabolites in DSS-induced colitis mice.GC-MSD results showed that 600 mg/kg SOA significantly reduced the levels of Lyxose,Ribose,Succinic acid,Phosphoric acid,and increased 4-hydroxyphenyl-Acetic acid level in the colon of colitis mice.Taurine and hypotaurine metabolism,Ascorbate and aldarate.metabolism,Alanine,aspartate and glutamate metabolism and Valine,leucine and isoleucine biosynthesis and other metabolic pathways were affected by 600 mg/kg SOA in colonic contents of colitis mice.Our data indicated that SOA relieved colitis by regulating colon metabolites and metabolic pathways in colitis mice.