抗癫痫药物治疗无效患者的差异表达基因谱生物信息学分析  

Bioinformatic Analysis of Differentially Expressed Genes Profiles in Patients with Ineffective Antiepileptic Drug Treatment

作　　者：姚承佼 李奕霖 熊钦 罗利红 谢凤娇 陈蕾[4] 冯培民[1] YAO Chengjiao;LI Yilin;XIONG Qin;LUO Lihong;XIE Fengjiao;CHEN Lei;FENG Peimin(Hospital of Chengdu University of Traditional Chinese Medicine,Chengdu 610072,Sichuan,China;Affiliated Hospital,North Sichuan Medical College,Nanchong 637007,Sichuan,China;North Sichuan Medical College,Nanchong 637007,Sichuan,China;West China Hospital,Sichuan University,Chengdu 610000,Sichuan,China)

机构地区：[1]成都中医药大学附属医院,四川成都610072 [2]川北医学院附属医院,四川南充637007 [3]川北医学院,四川南充637000 [4]四川大学华西医院,四川成都610000

出　　处：《辽宁中医杂志》2023年第7期1-7,I0001,共8页Liaoning Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金项目(81673854);南充市市校合作科研专项资金项目(19XHZ0153)。

摘　　要：目的通过生物信息学技术分析一线抗癫痫药物治疗无效的癫痫患者与治疗有效患者的基因芯片数据,筛选抗癫痫药物治疗无效相关的差异表达基因,探寻其下游生物学过程,预测西药治疗无效癫痫患者的潜在治疗中药。方法从基因表达数据库(GEO)提取数据集GSE143272基因芯片原始数据,使用GEO2R筛选抗癫痫药物无效与抗癫痫药物有效患者差异表达基因(DEGs)。利用在线分析软件DAVID对DEGs进行功能和信号通路的富集分析,String数据库构建蛋白互作网络。将DEGs与在线中药预测工具Coremine Medical相互映射,筛选治疗癫痫可能的靶向中药。结果丙戊酸钠治疗有效与治疗无效组筛选出DEGs 7个,卡马西平治疗有效与无效组筛选出DEGs 7个,苯妥英钠治疗有效与无效组筛选出DEGs 13个,其涉及的通路多与移植物抗宿主病、同种异体排斥反应、抗原处理和呈递等信号通路、自然杀伤细胞介导的细胞毒性、Th1/Th2细胞分化相关。筛选出的潜在中药以珍珠母、壁虎、南蛇藤、黄丝郁金、丹参、海狸香、天麻等定惊安神药,川芎、蕲蛇、香五加、川桐皮、艾纳香、白花丹等祛风通络药,茶树根、知母、白花蛇舌草、大黄、甘草、千金藤、忍冬藤、生地黄、蚕砂、水牛角等清热凉血药和厚朴、南沙参、大白部、瓜蒌、绞股蓝等祛痰药为主。结论抗癫痫药物治疗效果与基因差异表达密切相关,结果部分所述中药联合抗癫痫西药,可能提高抗癫痫治疗效果。Objective By using bioinformatics technology to analyze gene chip data of epilepsy patients who are ineffective in first-line anti-epileptic drug treatment and those who are effective in treatment,screen differentially expressed genes related to ineffective anti-epileptic drug treatment,explore their downstream biological processes and predict potential therapeutic effects of traditional Chinese medicine on epilepsy patients who are ineffective in Western medicine treatment.Methods Gene expression microarray datasets GSE143272 were downloaded from Gene Expression Omnibus(GEO)database.GEO2R was used to screen the DEGs.Pathway and functional enrichment analysis were performed by DAVID database.The protein-protein interaction(PPI)network was constructed by STRING.DEGs and the medical ontology information retrieval platform(Coremine Medical)were mapped to each other to screen the traditional Chinese medicines.Results 7 DEGs were identified between VPA-responders and non-VPA responders.7 DEGs were identified between CBZ-responders and non-CBZ responders.13 DEGs were identified between PHT-responders and non-PHT responders.The pathways involved were mostly related to graft-versus-host disease,allogeneic rejection,antigen processing and presentation,cytotoxicity mediated by natural killer cells and differentiation of Th1/Th2 cells.The potential traditional Chinese medicines include tranquilizing drugs,dispelling the wind drugs,cooling blood drugs and resolving phlegm drugs.Conclusion The effect of anti-epileptic drugs are closely related to gene differential expression.Combined the traditional Chinese medicine and anti-epileptic Western medicine,better results may be achieved.

关 键 词：癫痫 差异表达基因 耐药 中药预测 生物信息学 

分 类 号：R971.6[医药卫生—药品]