The mechanism of effect of Salidroside modulating gut flora in treating nonalcoholic fatty liver disease
Objective To explore the mechanism of action of Salidroside in the treatment of nonalcoholic fatty liver dis-ease(NAFLD)based on gut flora by using fecal microbiota transplantation(FMT).Methods Fourty NAFLD mice in-duced by 12 weeks of high-fat diet were randomly divided into normal group(Control group),model group(HFD group),Salidroside group(Sal group),FMT group of the model(HFD-FMT group)and FMT group of Salidroside(Sal-FMT group),with 8 mice in each group.Beginning from the 7th week,the mice in the Sal group were administered by gavage at a dose of 50 mg/(kg·d),those in the HFD-FMT group and Sal-FMT group were given fecal transplantation solution by gavage at a dose of 10 mL/(kg·d),and those in the Control group and HFD group were administered by gavage an equival-ent volume of physiological saline,for 6 weeks.(1)HE was used to observe the histopathological changes of liver and cal-culate the NAFLD Activity Score(NAS);(2)biochemical kit method was used to detect liver triglyceride(TG)content,serum aminotransferase(ALT,AST)activities and serum lipid(TG,TC,LDL-C,HDL-C)contents;(3)16S rRNA method was used to analyze gut flora diversity.Results Compared with the Control group,HFD group mice showed massive fat vacuoles with inflammatory cell infiltration in HE staining;and the body weight,liver weight,liver TG content,liver NAS score,serum ALT and AST activities and serum levels of TG,TC and LDL-C significantly increased(t=5.811,P＜0.001;t=2.278,P=0.020;t=6.505,P＜0.001;t=10.360,P＜0.001;t=3.559,P=0.002;t=3.836,P＜0.001;t=5.767,P＜0.001;t=3.314,P=0.003;t=3.972,P＜0.001);compared with the HFD group,Sal group mice showed alleviated hepatic lesions,and the liver TG content,liver NAS score and serum ALT activity significantly decreased(t=6.375,P＜0.001;t=7.095,P＜0.001;t=1.919,P=0.038);compared with the HFD-FMT group,Sal-FMT group mice showed alleviated hepatic le-sions,and the liver TG content,liver NAS score and serum ALT and AST activities significantly decreased(t=5.071,P＜0.001;t=8.775,P＜0.001;t=1.935,P=0.038;t=4.725,P＜0.001);compared with the HFD group,HFD-FMT group mice showed similar hepatic lesions,with no statistically significant differences in body weight,liver weight,liver TG con-tent,liver NAS score,serum ALT and AST activities and serum levels of TG,TC and LDL-C(t=0.337,P=0.741;t=0.408,P=0.690;t=0.428,P=0.675;t=0.798,P=0.438;t=0.323,P=0.752;t=1.671,P=0.117;t=0.606,P=0.555;t=0.496,P=0.627;t=0.174,P=0.864);compared with the Sal group,Sal-FMT group mice showed similar hepatic lesions,with no statistically significant differences in body weight,liver weight,liver TG content,liver NAS score,serum ALT and AST activities and serum levels of TG,TC and LDL-C(t=0.309,P=0.762;t=0.193,P=0.850;t=1.674,P=0.118;t=0.424,P=0.678;t=0.083,P=0.935;t=0.425,P=0.677;t=0.063 P=0.951;t=0.873,P=0.398;t=0.388,P=0.704).Furthermore,16S rRNA gut flora ana-lysis revealed that Salidroside changed the composition structure of gut flora and regulated the abundance of the flora.Conclusion Gut flora regulated by Salidroside is effective in treating NAFLD,and regulating the composition and abund-ance of gut flora may be the mechanism of the therapeutic effect of Salidroside.
万方数据
维普
