中国临床药理学杂志2024，Vol.40Issue(7)：1068-1071,4.DOI:10.13699/j.cnki.1001-6821.2024.07.028
基于网络药理学、分子对接和孟德尔随机化探讨拉莫三嗪抗重度抑郁症的作用机制
Exploring the mechanism of lamotrigine in treatment of major depressive disorder based on network pharmacology,molecular docking,and Mendelian randomization
摘要
Abstract
Objective To explore the mechanism of action of lamotrigine in the treatment of major depressive disorder(MDD).Methods Information on the drug targets of lamotrigine and the therapeutic targets of MDD were collected for intersection target gene analysis and protein-protein interaction screening.Various biological pathways related to lamotrigine in treatment of MDD were determined through gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis.The screened core targets were preliminarily validated using molecular docking technology.Further validation of Mendelian randomization was conducted using genome-wide association analysis data from gamma-aminobutyric acid recep tor-associated protein-like 1(GABARAPL1)and MDD in the OpenGWAS database.Results The biological pathways related to lamotrigine in treatment of MDD were identified,which included gamma-aminobutyric acid(GABA)ergic synapses,nicotine addiction,glutamatergic synapses,endogenous cannabinoid signaling.Molecular docking showed that the docking energy of lamotrigine with GABRA1,GABRB2,GABRA6,GABRD,GABRG2,GABRG1,GABRA5,GABRA4,GABRB3,and GABRA2 receptors was-5.8 kCal·mol-1.Among them,the GABRB3 receptor showed the strongest docking energy with lamotrigine,which was-9.5 kCal·mol-1.In the genome-wide association analysis data of GABARAPL1,303 single nucleotide polymorphisms were associated with GABARAPL1(P＜5 × 106).15 single nucleotide polymorphisms were screened and retained for Mendelian randomization analysis,and the results showed that GABA receptors may be an important therapeutic target for MDD.Conclusion The treatment of MDD with lamotrigine may be achieved by acting on GABA receptors,which provided a research basis for the clinical application of lamotrigine in treating MDD.关键词
拉莫三嗪/重度抑郁症/网络药理学/分子对接/孟德尔随机化Key words
lamotrigine/major depressive disorder/network pharmacology/molecular docking/mendelian randomization分类
药学引用本文复制引用
姜金生,陈红英,王伟权,胡海红,陈尧,欧阳冬生..基于网络药理学、分子对接和孟德尔随机化探讨拉莫三嗪抗重度抑郁症的作用机制[J].中国临床药理学杂志,2024,40(7):1068-1071,4.基金项目
国家自然科学基金资助项目(82073942) （82073942）
湖南省自然科学基金资助项目(2022JJ80097,2022JJ80113) （2022JJ80097,2022JJ80113）
