Effects Of Lactobacillus T3 On Oxidative Stress And Gut-liver Axis In Mice Of NAFLD With High-fat Dietary

High-fat diet has become the main diet in China,Europe and the United States and other countries.Obesity caused by high-fat diet has become a global health problem.It was found that obesity often leads to Nonalcoholic Fatty Liver Disease(NAFLD): obesity first causes simple steatosis of the Liver;with the accumulation of fat in Liver cells,Nonalcoholic steatohepatitis gradually forms,and even causes cirrhosis and even Liver cancer.The specific pathogenesis of obesity-induced NAFLD is not yet clear,and there is no effective treatment.Inflammatory responses and changes in autoimmune status caused by intestinal flora imbalance are related to oxidative stress in human liver and play an important role in the pathogenesis of NAFLD.Based on the theory of multiple shocks,relevant clinical and experimental evidence suggests that the "liver-gut axis" interaction is associated with the occurrence and development of NAFLD,and provides new ideas for the prevention and treatment of NAFLD.In this study,the probiotic strain Lactobacillus T3,which has a significant inhibitory effect on obesity induced by high-fat diet in Balb/c mice,and the watersoluble dietary fiber probiotics inulin were selected by the research group to study their effects on the basic and biochemical indexes of high-fat diet obese mice.The effect of high fat diet on liver oxidative stress and inflammation.To explore its effect on regulating intestinal flora and reducing LPS concentration in obese mice.To detect the expression of the intestinal epithelial tight junction protein in obese mice and verify whether probiotics and prebiotics can improve the liver injury caused by obesity through the "enteric-liver axis" approach.After giving high-fat diet mice Lactobacillus T3 and inulin for 6 weeks,the basic indexes and biochemical indexes such as TG,TC and LP could be significantly improved in obese mice,making them return to the normal level,P<0.05.Combined with MDA,AST and ALT related indexes of mouse liver oxidative stress and liver HE staining,it was found that Lactobacillus T3 and inulin intervention could relieve fat accumulation in the liver of mice with NAFLD and improve liver damage caused by high-fat diet.RT-PCR analysis of Nrf2 antioxidant pathway related expression factors in mouse liver showed that inulin intervention could significantly up-regulate Nrf2 pathway related factors,activate the expression of antioxidant enzyme system and inhibit oxidative stress in the liver of mice with high-fat diet,P<0.05.However,Lactobacillus T3 can only significantly increase BSEP gene expression,P<0.05,which may improve the oxidation-antioxidant imbalance caused by high-fat diet through bile acid circulation.RT-PCR analysis of mouse liver LPS/TLR-4 pathway and colonic tight junction protein showed that Lactobacillus T3 and inulin intervention could significantly reduce the LPS concentration in mouse liver and the expression of NF-?B related inflammatory factors downstream of TLR-4,P<0.05.The intervention of Lactobacillus T3 and inulin significantly increased the expression of tightly connected protein genes in mice colon tissue,P<0.05,and combined with colon HE staining,we speculated that the intervention of Lactobacillus T3 and inulin could improve the inflammatory dysfunction of NAFLD mice through the "enter-liver axis" approach.The diversity of intestinal flora in mice was analyzed by high-throughput sequencing.Both Lactobacillus T3 and inulin could change the composition of intestinal flora in high-fat diet mice,improve the diversity of intestinal flora in mice,and increase the ratio of Bacteroidetes to Firmicutes.It can be seen from the genus level that,after the intervention of Lactobacillus T3 and inulin,the intestinal tract production of acetic acid and butyrate bacteria in mice significantly increased,P<0.05,and short-chain fatty acid production bacteria may be the key bacteria influencing the liver injury of mice with high-fat diet NAFLD.