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-1 α signal 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-1α signaling 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-1α were 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-1 α signal pathway respectively and showed better affinity. Compared with the model group, the mRNA expression of AMPK, PGC-1 α in 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-1 α signal pathway to simulate the process of energy metabolism in vivo.

R285

国家自然科学基金项目（面上项目，重点项目，重大项目）