基于"肠-肝轴"探讨胃苓汤对代谢相关脂肪性肝病的改善作用OA

OBJECTIVE To investigate the ameliorative effect of Weiling decoction on metabolic associated fatty liver disease(MAFLD)based on the gut-liver axis theory.METHODS Male C57BL/6J mice were divided into a blank group(n=9)and a modeling group(n=47).The modeling group was fed a high-fat diet for 12 weeks to establish the MAFLD model.Forty-five modeled mice were randomly divided into a model group,a positive control group[metformin,0.2 g/(kg·d)],and Weiling decoction low-,medium-,and high-dose groups[6.17,12.34,24.68 g/(kg·d),calculated as crude drug],with 9 mice in each group.Mice in each group received intragastric administration of the corresponding drug solution or normal saline once daily for 4 consecutive weeks.After the last administration,the body weight,liver weight,and liver index were compared among groups;the levels of liver function indicators(alanine transaminase,aspartate transaminase),lipid indicators(total cholesterol,triglycerides,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol),inflammatory indicators[tumor necrosis factor-α,interleukin-6(IL-6),IL-1β],oxidative stress indicators(malondialdehyde,superoxide dismutase,glutathione peroxidase),and intestinal barrier indicators[lipopolysaccharide(LPS),diamine oxidase,D-lactic acid]were measured;hepatic pathological changes were observed;the expressions of tight junction proteins[zonula occludens-1(ZO-1),occludin]in jejunal tissue and proteins related to lipid metabolism[sterol regulatory element-binding protein-1(SREBP-1),fatty acid synthase(FASN),peroxisome proliferator-activated receptor α(PPARα)]and inflammatory pathways[Toll-like receptor 4(TLR4),myeloid differentiation primary response protein 88(MyD88),nuclear factor-κB p65(NF-κB p65)]in liver tissue were detected;and changes in gut microbiota were analyzed.RESULTS Compared with the model group,hepatic steatosis and inflammatory injury were significantly alleviated in all Weiling decoction dose groups;body weight(at week 16),liver weight,liver index,and the levels of liver function indicators,lipid indicators,inflammation indicators,oxidative stress indicators,and intestinal barrier indicators were all generally improved(P＜0.05).The expressions of SREBP-1,FASN,TLR4,and MyD88 and the phosphorylation level of NF-κB p65 in liver tissue were generally decreased or downregulated(P＜0.05),while the expressions of ZO-1 and occludin in jejunal tissue and PPARα in liver tissue were generally increased or upregulated(P＜0.05).Compared with the model group,the Observed species,Chao1,and Ace indices of gut microbiota in the Weiling decoction high-dose group were significantly increased(P＜0.05),and the relative abundances of Verrucomicrobiota,Akkermansia,etc.were significantly increased,while those of Actinomycetota,Alistipes,Faecalibaculum,etc.were significantly decreased(P＜0.05).CONCLUSIONS Weiling decoction can ameliorate MAFLD,and its effect may be associated with regulating gut microbiota,repairing the intestinal mechanical barrier,reducing LPS translocation,thereby inhibiting the TLR4/MyD88/NF-κB inflammatory pathway,alleviating oxidative stress,and regulating SREBP-1/FASN and PPARα-mediated lipid metabolism.