文献类型：期刊文献

中文题名：基于网络药理学及动物实验的杜仲腰痛丸治疗腰椎间盘突出症慢性下肢痛的作用研究

英文题名：Study on the Effect of Duzhong Yaotong Pill in the Treatment of lumbar Disc Herniation Based on Network Pharmacology and Animal Experiments

作者：陈祁青[1];马东[2];赵继荣[2];黄军凯[2];杨云云[2];朱宝[1];赵宁[1]

第一作者：陈祁青

机构：[1]甘肃省中医院,兰州730050;[2]甘肃中医药大学中医临床学院,兰州730030

第一机构：甘肃省中医院,兰州730050

年份：2023

卷号：25

期号：5

起止页码：1702

中文期刊名：世界科学技术-中医药现代化

外文期刊名：Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology

收录：CSTPCD;;北大核心:【北大核心2020】；CSCD:【CSCD_E2023_2024】；

基金：国家自然科学基金委员会地区科学基金项目(81760877):基于RS-fMRI及ERK-CREB-BDNF信号通路杜仲腰痛丸干预腰椎间盘突出症慢性疼痛的脑机制研究,负责人:赵继荣;甘肃省自然科学基金委员会创新基地和人才计划项目(17JR5RA051):纤维环源干细胞培养体系建立及中药诱导定向成纤维环细胞分化,负责人:陈祁青;甘肃省中医院博士启动基金项目(2018-1):纤维环源干细胞的体外分离培养、鉴定及生物学特性研究,负责人:陈祁青

语种：中文

中文关键词：杜仲腰痛丸;腰椎间盘突出症;网络药理学;动物实验;分子对接

外文关键词：Duzhong Yaotong pill;Lumbar disc herniation;Network pharmacology;Animal experiment;Molecular docking

摘要：目的通过对杜仲腰痛丸作用于腰椎间盘突出症慢性下肢痛大鼠模型镇痛效果动物实验的观察,并结合网络药理学及分子对接技术探讨其分子机制。方法以腰椎间盘突出症慢性下肢痛模型大鼠为研究对象,使用中药复方制剂杜仲腰痛丸对其进行干预,观察分析杜仲腰痛丸对模型大鼠的镇痛效应,并用TCMSP数据库检索并筛选获得杜仲腰痛丸的有效成分及其对应靶标,检索OMIM、GeneCards、DrugBank及PharmGkb数据库筛选合并获得腰椎间盘突出症疾病相关基因。利用Cytoscape_v3.8.0软件构建中药复方调控网络,通过STRING网络平台构建PPI网络关系并筛选出核心基因;然后进行GO与KEGG富集分析;最后利用AutoDock Vina软件进行分子对接。结果机械痛阈值组间比较,治疗组较正常组、模型组恢复快,差异有统计学意义(P<0.05);热痛阈值组间比较,治疗组较正常组、模型组恢复快,差异有统计学意义(P<0.05),且随着药物干预时间的延长,其治疗效果也越显著。网络药理学研究结果显示共筛选出335种有效成分、321个相关靶标以及90个药物治疗疾病的靶标;获得排名前5的关键成分(槲皮素、木犀草素、山柰酚、柚皮素、甘草查尔酮A)与9个核心靶标(JUN、MAPK14、RELA、MYC、FOS、TP53、MAPK1、STAT3、ESR1);共涉及2302条相关GO分子条目及157条信号通路;所有分子对接结果的最小结合能均小于-7.0 kcal·mol-1,具有强烈的结合活性。结论杜仲腰痛丸能够有效缓解腰椎间盘突出症慢性下肢痛大鼠模型的疼痛行为、改善其机械刺激与热刺激痛觉过敏现象,且可能是通过槲皮素、木犀草素、山柰酚等关键活性成分,作用于JUN、MAPK14、RELA等潜在核心靶点,调控PI3K-Akt、TNF等信号通路,从而发挥抗炎镇痛的效果。
Objective To observe the analgesic effect of Duzhong Yaotong Pill on chronic lower limb pain model rats with lumbar disc herniation through animal experiments,and to explore its molecular mechanism combined with network pharmacology and molecular docking technology.Methods The model rats of chronic lower limb pain caused by lumbar disc herniation were used as the research object.The traditional Chinese medicine compound preparation Duzhong Yaotong pill was used to intervene it.The analgesic effect of Duzhong Yaotong Pill on the model rats was observed and analyzed.The effective components and corresponding targets of Duzhong Yaotong pill were retrieved and screened by tcmsp database.OMIM,genecards The genes related to lumbar disc herniation were screened and obtained from drugbank and PharmGKB databases.Using Cytoscape_V3.8.0 software constructs the regulatory network of traditional Chinese medicine compound,constructs the PPI network relationship through the string network platform,and screens the core genes;Then go and KEGG enrichment analysis were carried out;Finally,the molecular docking was carried out by using autodock Vina software.Results Compared with the normal group and the model group,the mechanical pain threshold in the treatment group recovered faster(P<0.05);Compared with the heat pain threshold groups,the treatment group recovered faster than the normal group and the model group,and the difference was statistically significant(P<0.05).With the extension of the drug intervention time,the treatment effect was more significant.The results of network pharmacology research showed that 335 active ingredients,321 related targets and 90 targets for drug treatment were screened out;The top 5 key components(quercetin,luteolin,kaempferol,naringin,liquorice chalcone a)and 9 core targets(JUN,MAPK14,RELA,MYC,FOS,TP53,MAPK1,STAT3,ESR1)were obtained;A total of 2302 related go molecular entries and 157 signal pathways were involved;The minimum binding energy of all molecular docking results is less than-7.0 kcal/mol,which has strong binding activity.Conclusion Duzhong Yaotong pill can effectively alleviate the pain behavior of the rat model of chronic lower limb pain caused by lumbar disc herniation and improve the hyperalgesia caused by mechanical stimulation and thermal stimulation.It may act on the potential core targets such as Jun,Mapk14 and rela through the key active ingredients such as quercetin,luteolin and kaempferol,and regulate the PI3K Akt,TNF and other signaling pathways,so as to exert the anti-inflammatory and analgesic effects.