中药药理与临床2025，Vol.41Issue(7)：2-8,7.
荆防颗粒对高脂血症模型小鼠的影响及干预PPARα通路的机制探究
Effect of Jingfang(荆防)Granules on Hyperlipidemic Mouse Models and Exploration of Mechanism via PPARα Pathway Intervention
摘要
Abstract
Objective:To investigate the effects of Jingfang Granules(荆防颗粒)on lipid levels and inflammatory factors in two hyperlipidemic mouse models induced by egg yolk emulsion and high-fat emulsion and explore the potential mechanisms of action of Jingfang Granules through network pharmacology,focusing on the regulation of the peroxisome proliferator-activated receptor α(PPARα)signalling pathway.Methods:Potential active ingredients of Jingfang Granules were identified by using the TCMSP database and literature screening,and ingredi-ent targets were predicted through PubChem and Swiss target prediction databases.Hyperlipidemia-related targets were obtained from OMIM,GeneCard,and DisGeNET databases.The intersecting targets were obtained from Venny2.1.0 and input into the String database for construc-ting protein-protein interaction(PPI)networks.Kyoto encyclopedia of genes and genomes(KEGG)pathway analysis was performed using the DAVID database.A total of 30 SPF male KM mice were divided into the normal control group,egg yolk emulsion control group,20 mg/kg simvastatin group,and 10 and 15 g/kg Jingfang Granule groups,with six mice in each group.Mice received 10 days of corresponding drugs or solution by intragastric administration.On the 10th day,mice were injected intraperitoneally with 75%egg yolk emulsion(20 mL/kg)to es-tablish the model.12 h after administration,the serum contents of total cholesterol(TC),triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),and high-density lipoprotein cholesterol(HDL-C),as well as the activities of aspartate transaminase(AST)and alanine aminotrans-ferase(ALT)were detected.Another 50 SPF male mice were divided into the same five groups as above,with 10 mice in each group.Except for the normal control group,mice were daily given high-fat emulsions(20 mL/kg)to establish a model for continuous 21 days,while mice were treated with corresponding drugs or solution during modelling.The mice in the normal control group and model control group were given the same volume of solution.Samples were taken 12 h after the last administration,and the body mass,liver index,inguinal and epididymal fat index were detected.The serum and liver contents of TC,TG,LDL-C,and HDL-C,as well as serum AST and ALT activities were detected.Chemical methods were used to detect the serum and liver content of MDA.Enzyme linked immunosorbent assay(ELISA)was used to detect the liver levels of interleukin-6(IL-6),interleukin-10(IL-10),and tumor necrosis factor-α(TNF-α).Hematoxylin-eosin(HE)and oil red O staining were used to observe the morphological changes and lipid accumulation in the liver under a light microscope.Western blot(WB)method was used to detect the protein expressions of PPARα,3-hydroxy-3-methylglutaryl coenzyme A reductase(HMGCR),carnitine palmi-toyltransferase 1A(CPT1A),and cholesterol 7α-hydroxylase(CYP7A1)in the livers of mice.Results:Network pharmacology results showed the key targets of Jingfang Granules in hyperlipidemia treatment included IL6,TNF,EGFR,PPARG,PPARA,and IL10.KEGG revealed en-richment in lipid metabolism,lipids,atherosclerosis,and inflammation,involving signalling pathways such as PPAR and TNF.In animal ex-periments,compared with the egg yolk emulsion model group,Jingfang Granules significantly reduced the serum contents of TC,TG,and LDL-C,as well as the activities of ALT and AST(P<0.05 or P<0.01).Compared with the high-fat emulsion model group,Jingfang Granules sig-nificantly decreased serum and liver contents of TC,TG,and MDA,serum ALT activity and AST/ALT ratio,liver contents of LDL-C,TNF-α,and IL-6(P<0.05 or P<0.01)while increasing liver contents of HDL-C and IL-10(P<0.05 or P<0.01).Additionally,Jingfang Granules improved liver pathology and lipid accumulation,up-regulated the protein expressions of PPARα,CPT1A,and CYP7A1,and down-regulated HMGCR protein expression(P<0.05 or P<0.01).Conclusion:Jingfang Granules exhibit lipid-lowering effects in hyperlipidemic mouse models.The mechanism of action may be related to improving lipid metabolism and reducing the inflammation level via activating the PPARα signalling pathway,so as to intervene in hyperlipidemia.关键词
荆防颗粒/高脂血症/蛋黄乳液/高脂乳剂/过氧化物酶体增殖物激活受体α信号通路Key words
Jingfang(荆防)Granule/Hyperlipidemia/Egg Yolk Emulsion/High-Fat Emulsion/Peroxisome Proliferator-Activated Receptor α(PPARα)Signaling Pathway引用本文复制引用
黎斌,张雄伟,姜燕宁,丁美灵,包懿文,程国良,张贵民,曾南..荆防颗粒对高脂血症模型小鼠的影响及干预PPARα通路的机制探究[J].中药药理与临床,2025,41(7):2-8,7.基金项目
国家自然科学基金资助项目(编号:82074094) （编号:82074094）
成都中医药大学杏林学者项目(编号:QJJJ2022012). （编号:QJJJ2022012）
