摘要
目的研究天王补心丹(Tian Wang Bu Xin Dan,TWBXD)加减有效成分通过AMPK/PPAR/PGC-1α信号通路调控睡眠剥夺模型能量代谢的可能机制。方法通过中药系统药理学数据库及分析平台(TCMSP,Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform)、中国科学院上海有机化学研究所化学专业数据库(http://www.organchem.csdb.cn.)设定口服利用度(OB)≥30%、类药性(DL)≥0.18的筛选条件,检索下载TWBXD加减中所有中药的有效成分的分子结构;在RCSB PDB(RCSB Protein Data Bank)数据库中检索获取AMPK/PPAR/PGC-1α信号通路相关靶标蛋白的晶体结构;借助MOE(Molecular Operating Environment)软件,将受体与配体进行预处理及分子对接;20只雄性SPF级大鼠采用多平台水环境法模拟睡眠剥夺模型,每组10只,随机分为模型组、天王补心丹组(20 g·kg^(-1));一共予以4周的睡眠剥夺造模,后2周进行药物干预,模型组灌服等体积纯水;应用实时荧光定量聚合酶链式反应(Real-time PCR)检测AMPK、PPAR和PGC-1α的mRNA表达水平。结果筛选获得TWBXD加减组成的中药有效成分142种;分子对接结果表明,TWBXD有效成分能够分别与AMPK/PPAR/PGC-1α信号通路上的靶点相结合并展现出较好的亲和力;与模型组比较,天王补心丹组大鼠下丘脑中AMPK、PGC-1α的mRNA表达水平明显上升(P<0.05,P<0.01)。结论天王补心丹加减有效成分可通过特定位点与AMPK/PPAR/PGC-1α信号通路中的特定蛋白靶点结合模拟机体内能量代谢过程,发挥调控睡眠剥夺模型能量代谢的作用。
Objective To study the possible mechanism of the active components of Tianwang Buxin Pills(TWBXP)regulating energy metabolism through AMPK/PPAR/PGC-1αsignal pathway in sleep deprivation model.Methods Through the systematic pharmacology database and analysis platform of traditional Chinese medicine(TCMSP,Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform)and the chemistry database of Shanghai Institute of Organic Chemistry,Chinese Academy of Sciences(http://www.organchem.csdb.cn.),screening conditions of oral availability(OB)≥30%and drug-like(DL)≥0.18 was set to search and download the molecular structures of all the active components of traditional Chinese medicine in TWBXP addition and subtraction;The crystal structures of target proteins related to AMPK/PPAR/PGC-1αsignaling pathway were retrieved from the RCSB PDB(RCSB Protein Data Bank)database;the receptors and ligands were pre-processed and molecularly docked with the help of MOE(Molecular Operating Environment)software;20 male SPF rats were randomly divided into model group and TWBXP group(20 g·kg^(-1))using a multi-platform water environment to simulate sleep deprivation.The mRNA expression levels of AMPK,PPAR and PGC-1αwere measured by real-time PCR.Results 142 kinds of active components of modified TWBXP were screened,and the results of molecular docking showed that the effective components of TWBXP could combine with the targets of AMPK/PPAR/PGC-1αsignal pathway respectively and showed better affinity.Compared with the model group,the mRNA expression of AMPK,PGC-1αin the hypothalamus of TWBXP group increased significantly(P<0.05,P<0.01).Conclusion The active components of TWBXP can regulate the energy metabolism of sleep deprivation model by combining specific sites with specific protein targets in AMPK/PPAR/PGC-1αsignal pathway to simulate the process of energy metabolism in vivo.
作者
朱愽宽
黄晓宇
谢光璟
李浩
黄攀攀
Zhu Bokuan;Huang Xiaoyu;Xie Guangjing;Li Hao;Huang panpan(School of Basic Medicine,Hubei University of Chinese Medicine,Wuhan 430065,China;China Ship Scientific Research Center,Wuhan 430065,China)
出处
《世界科学技术-中医药现代化》
CSCD
北大核心
2021年第8期2681-2687,共7页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
国家自然科学基金委员会面上项目(81874414):养心安神法调控腺苷参与睡眠剥夺模型基底前脑能量代谢重构的机制研究,负责人:黄攀攀
武汉市科技局武汉市科技计划项目(2019020701011433):基于系统生物学的天王补心丹调控睡眠剥夺能量代谢重构机制研究,负责人:黄攀攀
关键词
天王补心丹
睡眠剥夺
能量代谢
分子对接
信号通路
Tianwang Buxin Pills
Sleep deprivation
Energy metabolism
Molecular docking
Signal pathway
作者简介
通讯作者:黄攀攀,博士,副研究员,硕士生导师,主要研究方向:中医药防治睡眠疾病研究。
