Mechanism Of Lactobacillus Reuteri In Alleviating Alcoholic Liver Injury In Mice Based On FXR Signaling Pathway

Objective: Based on Alcoholic Liver Disease(ALD)animal model,it is clear that Lactobacillus reuteri(L.reuteri)is involved in alleviating ALD.Screening target genes based on mouse liver transcriptomic data;Molecular biology techniques were used to elucidate the mechanism of FXR signal regulating axis-mediated L.reuteri in alleviating ALD progression.On this basis,an animal model was further constructed to clarify the role of FXR signal regulation axis,which provided a new scientific basis for the application of L.reuteri in the prevention and treatment of ALD.Methods: 1.The alcoholic liver disease mouse model was constructed by slow + rapid feeding,and the alcoholic liver disease mouse model was obtained after the intervention of L.reuteri.2.The effect of L.reuteri on alcoholic liver disease was determined by the preparation of pathological sections of mouse liver tissue or intestinal tissue and the detection of mouse serum biochemical indexes.3.Mouse liver tissues were collected for eukaryotic reference transcriptome sequencing;5.Screening target pathways based on transcriptomic data;6.The expression of related proteins was detected by western blotting.7.To further clarify the expression of target proteins by immunohistochemistry;8.Mice were given specific target inhibitors to determine the effect of the target.Results:1.Through the establishment of an animal model of alcoholic liver disease in mice and the detection of corresponding biochemical indexes and the preparation of pathological sections,it was found that L.reuteri had a alleviating effect on alcohol-induced lipid accumulation in liver;2.Analysis of reference transcriptomic sequencing data in eukaryotes showed that L.reuteri reversed alcohol-induced transcriptomic manifestations;3.Further data screening showed that the expression of genes related to lipid metabolism increased in L.reuteri group compared with model group;4.In order to target the target gene,further advanced analysis was conducted,and the results showed that the expression of Srebf1 was up-regulated,while the expression of Sirtuins family gene Sirt1 was down-regulated.5.By western blotting and immunohistochemistry,it was confirmed that the expressions of FXR,Srebf1 and Ch REBP in L.reuteri treatment group were up-regulated compared with the model group,while the expressions of CD36 were down-regulated.6.Mice were given Gly-β-MCA,an FXR inhibitor,by gavage,and the results showed that Gly-β-MCA could weaken the therapeutic effect of L.reuteri on ALD.Conclusion: 1.L.reuteri was given gavage during the establishment of the ALD animal model in mice,and the results showed that L.reuteri could alleviate alcoholic liver injury in mice.2.L.reuteri can reverse transcriptomic manifestations of alcoholic liver injury in mice.3.L.reuteri alleviates alcoholic liver injury in mice by up-regulating the expression of FXR signaling pathway.4.Gly-β-MCA,an FXR inhibitor,down-regulates the FXR signaling pathway and reduces the therapeutic effect of L.reuteri on alcoholic liver injury.