国医大师段富津教授经验方“三七-龙血竭”治疗高脂血症作用机制研究  

Mechanism research of experienced treatment"Sanqi-Longxuejie"for hyperlipidemia of professor Duan Fujin

作　　者：马伊笛 胡晓阳[1] 付殷 付强 MA Yi-di;HU Xiao-yang;FU Yin;FU Qiang(School of Basic Medical Sciences,Heilongjiang University of Chinese Medicine,Harbin 150040,China)

机构地区：[1]黑龙江中医药大学基础医学院,黑龙江哈尔滨150040

出　　处：《时珍国医国药》2024年第6期1482-1487,共6页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金面上项目(81874426);李冀教授全国名中医工作室项目;黑龙江中医药大学研究生创新科研项目(2022yjscx014)。

摘　　要：目的以网络药理学及分子对接技术结合动物实验验证探讨三七-龙血竭治疗高脂血症的作用机制。方法通过网络药理学方法对三七-龙血竭配伍治疗高脂血症作用机制进行预测并结合分子对接进行初步验证;高脂饲料喂养构建高脂血症小鼠模型,油红染色法观察小鼠肝组织脂质沉积情况,酶联免疫吸附(ELISA)法及蛋白免疫印记(Western Blot)法检测小鼠血脂四项水平及网络药理学结果中关键通路相关蛋白表达情况以验证三七-龙血竭治疗高脂血症作用机制。结果网络药理学筛选得到包括槲皮素、甘草素、柚皮素等共17个三七-龙血竭活性成分,对应靶点471个,疾病靶点2502个,药物与疾病共有靶点158个,包括AKT1、VEGFR、EGFR、CASP3、PPARG等核心靶点;GO富集分析得到类固醇代谢、激酶活性调节、脂质代谢调节等2134个生物过程,膜筏、膜微域、囊泡腔等87个细胞组分,核受体活性、类固醇结合、单羧酸结合等209个分子功能;KEGG富集分析得到PI3K-AKT、HIF-1、MAPK等163条通路;分子对接结果显示槲皮素等五个核心成分与AKT1等五个核心靶点均具有较高结合能;动物实验结果表明,三七-龙血竭可有效减轻模型小鼠肝组织脂质沉积,调节小鼠血脂水平,抑制肝组织中脂代谢酶HMGR活性及PI3K、p-AKT、SREBP2蛋白表达。结论三七-龙血竭配伍可通过调控PI3K/AKT/SREBP2信号通路相关蛋白表达调节高脂血症小鼠脂代谢功能,进而改善小鼠血脂水平。Objective To investigate the mechanism of action of Sanqi-Longxuejie in the treatment of hyperlipidemia by network pharmacology and molecular docking technology combined with animal experiments.Methods The mechanism of action of Sanqi-Longxuejie in the treatment of hyperlipidemia was predicted by network pharmacology and preliminarily verified by molecular docking.A mouse model of hyperlipidemia was constructed by high-fat feed feeding,lipid deposition in liver tissues of mice was observed by oil red staining,and the expression of key pathway-related proteins in the four levels of blood lipids and network pharmacology was detected by enzyme-linked immunosorption(ELISA)and Western Blot,so as to verify the mechanism of action of Panax notoginseng-dragon's blood exhaustion in the treatment of hyperlipidemia.Results A total of 17 active ingredients of Sanqi-Longxuejie,including quercetin,glycyrrhizin and naringenin,were screened by network pharmacology,corresponding to 471 targets,2502 disease targets,and 158 drug and disease targets,including AKT1,VEGFR,EGFR,CASP3,PPARG and other core targets.GO enrichment analysis yielded 2134 biological processes such as steroid metabolism,kinase activity regulation,lipid metabolism regulation,87 cell components such as membrane raft,membrane microdomain,vesicle cavity,and 209 molecular functions such as nuclear receptor activity,steroid binding,and monocarboxylic acid binding.KEGG enrichment analysis yielded 163 pathways,including PI3K-AKT,HIF-1,and MAPK.The results of molecular docking showed that the five core components such as quercetin and the five core targets such as AKT1 had high binding energy.The results of animal experiments showed that Panax notoginseng blood depletion could effectively reduce lipid deposition in liver tissues of model mice,regulate blood lipid levels,inhibit the activity of lipid metabolism enzyme HMGR and the expression of PI3K,p-AKT and SREBP2 proteins in liver tissues.Conclusion Sanqi-Longxuejie can regulate the lipid metabolism function of hyperl

关 键 词：三七 龙血竭 高脂血症 网络药理学 分子对接 实验验证 

分 类 号：R249.2[医药卫生—中医临床基础] R249.7[医药卫生—中医学]