基于网络药理学与动物实验验证降脂轻身胶囊调控PPARα通路治疗高脂血症的作用机制OA

Objective:To investigate the therapeutic mechanism of Jiangzhiqingshen(降脂轻身)capsules for hy-perlipidaemia based on network pharmacology and animal experiments.Methods:The possible targets of Jiangzhiqingsh-en capsules for hyperlipidaemia were obtained through network pharmacology,and the core targets were subjected to gene ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment a-nalysis for screening of the biological processes and signaling pathways that might be involved.Fifty mice were randomly assigned into normal control,model control,Jiangzhiqingshen capsules(2.4 g/kg and 0.6 g/kg),and rosuvastatin(1.3 mg/kg)groups.A hyperlipidemia model was established by feeding with a high-fat diet.After 10 weeks of phar-macological interventions,the body mass,liver mass,liver index,and Lee's index were weighed or calculated.His-topathological changes of the liver tissue were observed by hematoxylin-eosin(HE)staining and oil red O staining.Ser-um levels of biochemical indexes were measured by biochemical kits,and real-time PCR and Western blot were used to determine the mRNA and protein levels,respectively,of peroxisome proliferator-activated receptor alpha(PPARα),per-oxisome proliferator-activated receptor gamma coactivator-1 alpha(PGC-1α),acyl-CoA oxidase 1(ACOX1),and carni-tine palmitoyltransferase 1 alpha(CPT1α).Results:A total of 787 targets related to the components of Jiangzhiqingshen capsules,341 lipid marker-related targets,and 2 060 disease-related targets were screened by network pharmacology,with 39 common targets.GO functional enrichment and KEGG enrichment analysis suggested that Jiangzhiqingshen capsules exerted therapeutic effects via fatty acid β-oxidation,and the PPARα signaling pathway might be one of the action path-ways.The results of animal experiments showed that compared with the normal control group,the model control group showed increased body mass,liver wet mass,liver index,and Lee's index(P＜0.05),raised serum levels of total choles-terol(TC),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),alanine aminotransferase(ALT),and as-partate aminotransferase(AST)but declined serum level of high-density lipoprotein cholesterol(HDL-C)(P＜0.05),inflammatory infiltration,necrotic foci,and increased lipid deposition in the liver tissue,and down-regulated expression levels of PPARα,PGC-1α,CPT1α,and ACOX1(P＜0.05).Compared with the model control group,Jiangzhiqingshen capsules decreased the body mass,liver wet mass,liver index,and Lee's index(P＜0.05),lowered the serum levels of TC,TG,LDL-C,ALT,and AST(P＜0.05),alleviated the hepatic inflammation and lipid deposition,and up-regulated the expression levels of PPARα,PGC-1α,CPT1α,and ACOX1 in the liver tissue(P＜0.05).Conclusion:Jiangzhiqingshen capsules can restore the blood lipid levels and the liver function in hyperlipidemic mice by up-regulating the PPARα pathway in the liver tissue to promote the expression of downstream proteins(PGC-1α,CPT1α,and ACOX1)and en-hance fatty acid β-oxidation.