基于网络药理学-分子对接及实验研究探讨黄连解毒汤治疗有机磷中毒的作用机制  

Mechanism of Huanglian Jiedu Decoction(黄连解毒汤)in the Treatment of Organophosphorus Pesticide Poisoning Based on Network Pharmacology-Molecular Docking and Experimental Verification

作　　者：王晓凤[1] 郑强[1] 王林[1] 张红雷[1] 赵敏[1] WANG Xiaofeng;ZHENG Qiang;WANG Lin;ZHANG Honglei;ZHAO Min(Second Emergency Department,Shengjing Hospital of China Medical University,Shenyang 110000)

机构地区：[1]中国医科大学附属盛京医院第二急诊科,沈阳110000

出　　处：《中药药理与临床》2023年第8期19-25,共7页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金面上项目(编号:81671898)。

摘　　要：目的:采用网络药理学-分子对接的方法,探讨黄连解毒汤治疗有机磷中毒(OPP)的作用机制,并进行动物实验验证分析。方法:利用网络药理学工具,获得黄连解毒汤治疗有机磷中毒(OPP)的有效成分、核心靶点和信号通路。建立有机磷中毒(OPP)大鼠模型,进行病理染色、ELISA、PCR实验验证网络药理学预测的主要靶点以及治疗效果。结果:网络药理学筛选出黄连解毒汤关键有效成分包括槲皮素、掌叶防己碱、山柰酚;核心靶点涉及MTOR、SRC、ESR1、AKT1、STAT3、BCL2L1;GO数据富集分析发现,乙酰胆碱分解代谢过程、骨骼肌卫星细胞的增殖依赖性的正向调控生长因子、生物碱代谢、促进复合物依赖性分解代谢过程、UA反应、等在生物过程中富集度较高;乙酰胆碱酯酶活性、JUN激酶活性、胆碱酯酶活性、四氢生物蝶呤结合、羧酸跨膜转运体活性、等在分子功能中富集度较高;主轴突、染色体移动复合体、质膜外侧面、BCL2家族蛋白复合物、核包膜腔、等在细胞组成中富集度较高。KEGG通路富集分析内分泌抵抗、催乳素信号通路、膀胱癌、EGFR酪氨酸激酶抑制剂耐药性、Erbb信号通路、等可能在黄连解毒汤治疗有机磷中毒(OPP)中起关键作用;分子对接验证各核心靶点与其对应化合物之间均有较强的结合力,其中以MTOR和槲皮素、SRC和山柰酚、STAT3和槲皮素之间结合能最低,结合最为稳定。动物实验表明,与正常对照组比较,模型对照组中大鼠血清IL-4、IL-6、TNF-α含量明显升高,肺组织Mtor、Src、Stat3的mRNA表达明显上调(P<0.05);与模型对照组相比,常规治疗组大鼠血清中IL-4、IL-6、TNF-α含量明显下降,肺组织Mtor、Src、Stat3的mRNA表达明显下调(P<0.05);与常规治疗组相比,黄连解毒汤联合治疗组能进一步明显改善肺组织病理变化,降低血清中IL-4、IL-6、TNF-α含量,明显下调肺组织Mtor、Src、Stat3的mRNA表Objective:To explore the mechanism of Huanglian Jiedu Decoction(黄连解毒汤)in the treatment of organophosphorus pesticide poisoning(OPP)through network pharmacology and molecular docking and validate and analyze the results through animal experiments.Methods:Network pharmacology was used to obtain the active ingredients,core targets,and signaling pathways of Huanglian Jiedu Decoction in the treatment of OPP.An OPP rat model was established,and pathological staining,ELISA,and PCR experiments were conducted to validate the main predicted targets of network pharmacology and the therapeutic effects.Results:Network pharmacology screening identified key active ingredients of Huanglian Jiedu Decoction,including quercetin,palmatine,and kaempferol.The core targets involved MTOR,SRC,ESR1,AKT1,STAT3,and BCL2L1.GO data enrichment analysis revealed higher enrichment in biological processes such as acetylcholine catabolic process,growth factor-dependent positive regulation of satellite cell proliferation in skeletal muscle,alkaloid metabolism,complex-dependent catabolic process,and UA reaction.Higher enrichment was observed in molecular functions such as acetylcholinesterase activity,JUN kinase activity,cholinesterase activity,tetrahydrobiopterin binding,and carboxylic acid transmembrane transporter activity.In cellular components,higher enrichment was found in axon,chromosome movement complex,plasma membrane outer surface,BCl2 family protein complex,and nuclear envelope lumen.KECG pathway enrichment analysis suggested that endocrine resistance,prolactin signaling pathway,bladder cancer,ECFR tyrosine kinase inhibitor resistance,and ERBB signaling pathway may play key roles in the treatment of OPP with Huanglian Jiedu Decoction.Molecular docking confirmed strong binding affinity between each core target and its corresponding compound.Among them,the binding affinity between MTOR and quercetin,SRC and kaempferol,and STAT3 and quercetin were the lowest,indicating the most stable binding.Animal experiments showed that compared

关 键 词：黄连解毒汤 有机磷中毒 网络药理学 分子对接 作用机制 

分 类 号：R285.5[医药卫生—中药学]