| The global incidence of non-alcoholic fatty liver disease(NAFLD)has increased year by year,but the pathogenesis of NAFLD has not yet been fully clarified.There is no effective means of treating NAFLD in medicine,so it is urgent to find a way to prevent and treat NAFLD.Previous studies have found that sulforaphane(SFN)could improve liver lipid metabolism disorders caused by high-fat diet.As a food-borne bioactive ingredient,SFN is expected to be effective in improving various metabolic syndromes such as NAFLD,diabetes,and obesity.In this study,gut microbiota and bile acids were taken as the starting point to explore the mechanism of intestinal-hepatic circulation of bile acids and the regulation of SFN on bile acid metabolism,hoping to provide scientific evidence for the treatment and intervention of NAFLD.A rat model of NAFLD was established by high-fat diet,divided into control group(CON),high-fat model group(HFD),low-dose SFN intervention group(L),medium-dose SFN intervention group(M),high-dose SFN intervention group(H).Through histopathological examination of liver,determination of TC and TBA,determination of serum bile acid spectrum and determination of serum taurine content,it was found that SFN could alleviate hepatocyte injury in NAFLD rats,reduce serum total cholesterol(TC)and total bile acids(TBA)levels,improve the imbalance of serum bile acid ratio in rats induced by high-fat diet,up-regulate the ratio of CA,?MCA,UDCA,HDCA in serum bile acid profile,down-regulate the ratio of ?MCA,?MCA,TCNCA,T?MCA,DCA and LCA,reduce the toxic effects of hydrophobic bile acids DCA and LCA on the body and improve lipid metabolism.High-fat diet led to increased levels of CDCA,?MCA,?MCA,DCA,LCA,TCDCA,and T?MCA,and SFN could reduce its content and improve cholestasis.The serum taurine content of NAFLD rats decreased,and the serum taurine content increased after SFN intervention.Through real-time fluorescent quantitative PCR technology,it was found that SFN had an improved effect on the gut microbiota.SFN intervention could increase the number of Lactobacillus,Bacteroides fragilis and Bifidobacterium with BSH activity,increase the number of Clostridium cluster XI with 7? dehydroxylase activity,reduce the number of Bilophila wadsworthia and Escherichia coli related to taurine metabolism.SFN could improve bile acid metabolism and intestinal hepatic circulation by real-time fluorescent quantitative PCR,Western Blotting and ELISA.SFN increased the expression of CYP7A1 mRNA and protein,decreased the expression of CYP27A1 mRNA and protein,increased the expression of BSEP mRNA in liver efflux transporter,decreased the expression of NTCP and OATP1 mRNA in liver transporters,decreased the expression of ASBT mRNA in ileum reabsorption transporter.increased the expression of ileum transporter IBABP,ileum efflux OST? and OST? mRNA,reduced the accumulation of bile acids in hepatocytes and ileal epithelial cells,reduced the damage of liver and intestine caused by cholestasis;inhibited the expression of FXR and SHP mRNA and protein in liver,activated LRH-1 mRNA and protein expression,activated ileum FXR,FGF15,FGFR4 mRNA and protein expression,and regulated liver and ileal FXR signaling pathways.In summary,SFN could improve rat NAFLD by regulating rat serum bile acid profile,gut microbiota,and bile acid synthesis,transport and FXR regulatory pathways. |
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