人参皂苷Rb1通过调节肠-肝轴改善非酒精性脂肪性肝炎的作用及机制研究OA

Objective To investigate the therapeutic effects of ginsenoside Rb1 on non-alcoholic steatohepatitis(NASH)and its mechanisms through modulating gut microbiota and repairing intestinal barriers in liver inflammation and metabolic disorders.Methods A model NASH mouse was established by high-fat,high-cholesterol diet(HFHCD)feeding.After modeling,the NASH mice were treated with Rb1 via intraperitoneal injection.An in vitro NASH model was induced with oleic acid+cholesterol in HepG2 cells.Serum biochemistry,histopathological observation(HE,Oil Red O,Masson,Sirius Red staining),and Western blotting(inflammatory and tight junction proteins)were performed.Gut microbiota was analyzed with 16S rRNA gene sequencing.The correlations between key microbiota and metabolic phenotypes were analyzed using Spearman correlation analysis and SHapley Additive exPlanations(SHAP)analysis.Results Rb1 significantly reduced serum levels of total cholesterol(TC),triglyceride(TG),alanine transaminase(ALT),aspartate aminotransferase(AST)and low-density lipid-cholesterol(LDL-C)in the NASH mice(P<0.05),decreased lipid accumulation and fibrosis in liver tissues,inhibited TNF-α and IL-1β expression,and increased zonula occludens-1(ZO-1)and Occludin levels(P<0.05).It also boosted beneficial bacteria like Lactobacillus and Bifidobacterium,reduced harmful bacteria such as Desulfovibrio,and enhanced gut microbiota diversity(P<0.05).Correlation analysis showed that beneficial bacteria enriched by Rb1 were positively correlated with the improvements of metabolic indicators and negatively with inflammatory factors and liver injury markers(P<0.05).The machine learning model identified ALT as the key predictor for NASH.Conclusion Rb1 can inhibit inflammatory response and improve lipid metabolism by modulating gut microbiota and repairing the intestinal barrier,and thus significantly alleviate NASH progression.