基于网络药理和动物实验探讨活血通络方治疗脊髓损伤的作用机制  

Exploring the mechanism of action of Huoxue Tongluo prescription for the treatment of spinal cord injury based on network pharmacology and molecular docking technology

作　　者：王佳星 陈家扬 申婷婷 王智慧[2,3] 任晓平 WANG Jiaxing;CHEN Jiayang;SHEN Tingting;WANG Zhihui;REN Xiaoping(Department of Medicine School,Guangxi University,Nanning 530004,China;Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine,Nanning 530011,China;Guangxi University of Chinese Medicine,Nanning 530200,China)

机构地区：[1]广西大学医学院,南宁530004 [2]广西中医药大学附属瑞康医院,南宁530011 [3]广西中医药大学,南宁530200

出　　处：《中国实验动物学报》2025年第1期1-13,共13页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然科学基金(82060874);广西重点研发计划项目(桂科AB21196062);广西中医药大学2023年研究生教育创新计划项目(YCSY2023042)。

摘　　要：目的采用网络药理学、分子对接技术和体内实验,探讨活血通络方(Huoxue Tongluo prescription,HXTLP)治疗脊髓损伤(spinal cord injury,SCI)的潜在作用机制。方法通过中药系统药理学数据库与分析平台(TCMSP)检索HXTLP的活性成分,瑞士化合物靶点预测数据库(Swiss target prediction)获取作用靶点,构建“活性成分-靶点”网络。SCI相关靶点通过访问在线人类孟德尔遗传数据库(OMIM)和人类基因数据库(GeneCards)获得。基于基因与蛋白质相互作用网络分析数据库(STRING)建立HXTLP与SCI共同靶点的蛋白互作网络(PPI)。Metascape数据库用于京都基因与基因组百科全书(KEGG)和基因本体(GO)富集分析共同靶点,Autodock 1.5.7软件进行活性成分与关键靶点的分子对接,Pymol 2.4.0软件进行结果可视化。最后通过动物实验验证HXTLP治疗SCI的效果。结果研究共获得184个交集靶点,关键靶点涉及丝氨酸/苏氨酸激酶1(serine/threonine kinase 1,AKT1)、信号传导及转录激活蛋白3(signal transducer and activator of transcription 3,STAT3)、热休克蛋白90α家族A类成员1(heat shock protein 90 kDa alpha,class A member 1,HSP90AA1)、磷脂酰肌醇4,5-二磷酸3-激酶催化亚基-α(phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha,PIK3CA)、磷酸肌醇3激酶调节亚基1(phosphoinositide-3-kinase regulatory subunit 1,PIK3R1)、GTP酶(harvey ras,HRAS)、雌激素受体1(estrogen receptor 1,ESR1)、丝裂原活化蛋白激酶1(mitogen-activated protein kinase 1,MAPK1)、表皮生长因子受体(epidermal growth factor receptor,EGFR)等。分子对接结果表明核心活性成分和关键靶点之间具有较高的结合亲和力。动物实验结果显示,与模型组相比,活血通络方组小鼠行为学评分升高(P<0.05),后肢运动功能改善,损伤区域组织学形态更完整。蛋白免疫印迹(Western Blot)结果显示HXTLP可有效的抑制关键靶点蛋白HSP90AA1和磷酸化STAT3(phospho-STAT3,P-STAT3)Objective This study preliminarily investigated the potential mechanisms of the Huoxue Tongluo prescription(HXTLP)in treating spinal cord injury(SCI)through a combination of network pharmacology,molecular docking technology,and in vivo experimental verification.Methods The traditional Chinese medicine systems pharmacology database and analysis platform(TCMSP)were utilized to select the active ingredients,targets of action were obtained from Swiss target prediction database,and an“active ingredients-targets”network was constructed.SCI-related targets were obtained by accessing online mendelian inheritance in man(OMIM)and human gene database(GeneCards),and a protein interaction network of the common targets of HXTLP and SCI was established based on the search tool for the retrieval of interacting genes/protein(STRING)database.The Metascape database was used in KEGG pathway enrichment and GO analyses of the common targets.Molecular docking of active ingredients and key targets was performed through Autodock 1.5.7 software,and the results were visualized with Pymol 2.4.0 software.Finally,the effect of HXTLP on SCI was verified by animal experiments.Results A total of 184 intersection targets were obtained,and the key targets were serine/threonine kinase(AKT1),signal transducer and activator of transcription 3(STAT3),heat shock protein 90 kDa alpha,class A member 1(HSP90AA1),phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA),phosphoinositide-3-kinase regulatory subunit 1(PIK3R1),harvey ras(HRAS),estrogen receptor 1(ESR1),mitogen-activated protein kinase 1(MAPK1),and epidermal growth factor receptor(EGFR).Molecular docking result showed strong binding abilities between the core active components and key targets.In the animal experiments,the behavioral scores of mice in the HXTLP group increased(P<0.05),the motor function of hind limbs was improved,and the histological morphology of the injured area was more complete compared with those of the model group.Western Blot result revealed that

关 键 词：活血通络方 脊髓损伤 网络药理 分子对接 动物实验 

分 类 号：Q95-33[生物学—动物学]