| Nonalcoholic fatty liver disease(NAFLD)is a clinicopathological syndrome characterized by a large amount of fat accumulating in hepatocytes,which is caused by nonalcoholic factors and other unknown causes.The prevalence of NAFLD is increasing all over the world,which has become a global health problem,and there is no effective drug and treatment for NAFLD.Recent studies have shown that probiotics can improve NAFLD by interfering with intestinal flora,but the mechanism of its regulation and action is not clear.In this study,the NAFLD model of SD rats was constructed to evaluate the effect of Lactobacillus plantarum MA2 selected by our research group in the early stage,and to further study the clear correlation mechanism between probiotics intestinal microecology NAFLD disease.It can provide new strategies and valuable information for probiotics to improve and prevent NAFLD,and lay an important theoretical foundation for probiotics in clinical use.The results showed that the probiotic Lactobacillus plantarum MA2 not only effectively improved the appearance and weight of rats caused by NAFLD disease,improved the appearance and phenotype of rats’ liver,reduced the liver index,but also reduced the large oil drops and small fat drops distributed in the liver tissue,improved the swelling of liver cells,nuclear deviation,inflammatory cell infiltration,reduced the denaturation and small size of fat.It also improved the levels of GPT,got,TC and TG in serum.Through further study,it was found that the content of Lactobacillus,ruminococcae UCG-005,ruminococcae-014,Escherichia-Shigella,blautia,Bacteroides and other bacteria in the intestine of rats were significantly reduced.The content of Eubacterium and coprostanogenes increased the level of beneficial bacteria,decreased harmful bacteria,increased the total number of species,richness and biodiversity of intestinal flora in rats,and enhanced the species specificity.Moreover,according to the prediction results of picrust function,Lactobacillus plantarum MA2 played a role in improving the intestinal microecology of rats.In addition,supplementation of probiotic Lactobacillus plantarum MA2 improved the intestinal mucosal barrier system in rats with NAFLD disease induced by MCD(methionine-choline-deficient)diet,and the expression of Claudin-1 in intestinal epithelium significantly reduced the LPS level in rats,inhibited the activation of TLR4-MyD88 signaling pathway,and thus reduced the activation of downstream NF KB signaling pathway and JNK signaling pathway.It not only inhibited the activity of NF-kBp65 protein,but also decreased the relative transcription level of TNF-α,IL-1 β,IL-6,anti-inflammatory cytokines IL-4,IL-10,and slowed down the inflammatory response.It also inhibited the activity of JNK,slowed down the inflammatory response,and at the same time,made AP-1 protein located at the downstream of JNK signaling pathway at the relative transcription level.It can reduce the apoptosis and pathological changes of liver cells,and reduce the accumulation of lipid in liver cells.In conclusion,the probiotic Lactobacillus plantarum MA2 isolated and preserved in our laboratory can improve NAFLD disease by regulating intestinal microecological environment,and then by affecting TLR4-MyD88,NF KB,JNK signal pathway. |