The Ameliorative Effects And Mechanisms Of Probiotic Bifidobacterim V9 On Non-alcoholic Fatty Liver Disease Induced By High-fat Diet In Rats

Nonalcoholic fatty liver disease(NAFLD is a chronic metabolic liver disease of clinicopathological syndrome,which is caused by factors excluding alcohol and other known hepatotoxic drugs.NAFLD is a multifactorial disease with complex pathogenesis.At present,the clinical drugs against NAFLD is mainly hypolipidemic drugs combined with hepatic protectants or antioxidant.However,the safety and efficacy of these drugs still need to be further evaluated.Therefore,it is of great significance to study the pathogenesis of nonalcoholic fatty liver and to look for effective drugs against the development of NAFLD.The protective effects and mechanisms of Bifidobacterium V9 on NAFLD induced by high-fat diet were studied in this study.Forty male Wister rats of about 120g were randomly divided into five groups,namely,blank group(Control),model group(HFD),berberine positive drug group(Berberine),probiotic V9 treatment group(HFD/V9),probiotic V9 control group(V9).The blank group and the V9 control group were given normal maintenance diet,while the other rats were fed with a high-fat diet for six weeks.After six weeks,all the groups of rats were given normal maintenance diet.The positive drug group was administered with berberine 300mg/kg.HFD/V9 and V9 group were orally given 1×10~9 CFU/ml Bifidobacterium V9.Four weeks later,rats were fasted for 12h and then sacrificed.Blood,liver and intestinal tissues were collected.Serum levels of ALT,AST,fasting blood glucose and TC,and levels of liver glycogen,TC,TG and FFA in serum were detected.The pathological damage of liver tissue was observed by HE staining.The expression levels of IL-6,IL-1 beta and TNF-alpha in serum and liver were measured.The expression level of Toll like receptor(TLRs)and lipid metabolism related genes SREBP-1c and FAS mRNA were detected by Real-time PCR.Western blot was used to detect the expression of PPAR-γ,p-AMPK,p-AKT,p-JNK,p-ERK and p-NF-κB in liver tissues.The results showed that probiotic V9 could significantly reduce high fat diet-induced ALT,AST,TC,TG,FFA and blood glucose levels.The expression of IL-6,IL-1βand TNF-αin serum and liver tissues was also decreased after V9 treatment.HE staining showed that probiotics V9 could effectively alleviate liver injury induced by high-fat diet.Probiotics V9 significantly inhibited m RNA levels of SREBP-1c,FAS and PPAR-αin the liver.At the same time,the mRNA level of ASC and NLRP3 decreased significantly.Probiotics V9 promoted the activation of p-AMPK protein levels in liver tissues.Western blotting showed that probiotics V9 inhibited the expression of TLR4 and the phosphorylation of AKT,JNK,ERK and NF-kappa B.This study indicates that probiotics V9 can alleviate the symptoms of NAFLD by regulating the AMPK/PPAR signaling pathway and TLR4/NLRP3 signaling pathway.