左慈丸的化学成分及治疗围绝经期听力损失的作用机制研究:基于网络药理学与分子对接技术  

Chemical Composition and Mechanism of Zuoci Pill in Treating Perimenopausal Hearing Loss Based on Network Pharmacology and Molecular Docking Technology

作　　者：刁翯 白文佩 赵立东[3] DIAO He;BAI Wenpei;ZHAO Lidong(Department of Traditional Chinese Medicine,Tianjin Central Hospital of Gynecology Obstetrics/Nankai University Maternity Hospital/Tianjin Key Laboratory of Human Development and Reproductive Regulation,Tianjin 300199,China;Department of Obstetrics and Gynecology,Beijing Shijitan Hospital,Capital Medical University,Beijing 100038,China;Academy of Otolaryngology-Head and Neck Surgery,Chinese PLA General Hospital/National Clinical Research Center for Otolaryngologic Diseases/State Key Lab of Hearing Science Affiliated to Chinese Ministry of Education/Beijing Key Lab of Hearing Impairment Prevention and Treatment,Chinese PLA Medical School,Beijing 100853,China)

机构地区：[1]天津市中心妇产科医院南开大学附属妇产医院中医科天津市人类发育与生殖调控重点实验室,300199 [2]首都医科大学附属北京世纪坛医院妇产科,北京市100038 [3]中国人民解放军总医院耳鼻咽喉头颈外科医学部耳鼻喉科国家耳鼻咽喉疾病临床医学研究中心聋病教育部重点实验室聋病防治北京市重点实验室中国人民解放军医学院,北京市100853

出　　处：《中国全科医学》2024年第12期1493-1503,共11页Chinese General Practice

基　　金：国家自然科学基金青年基金资助项目(82004409);天津市医学重点学科(专科)建设项目(TJYXZDXK-039A);北京市自然科学基金资助项目(7202075)。

摘　　要：背景近年来,围绝经期听力损失(PMS-HL)症状得到普遍关注,但无针对性治疗。左慈丸治疗耳聋已有百年历史,但尚无该药治疗PMS-HL的相关研究。目的在网络药理学和分子对接技术的基础上,进一步通过动物实验验证,初步探讨左慈丸对PMS-HL的作用机制及治疗靶点。方法检索数据库时限均为建库至2023年2月。根据左慈丸的组方,通过TCMSP和Uniprot数据库挖掘该药物活性成分和作用靶点,根据GeneCards、OMIM、TTD、DrugBank、PharmGKB数据库获取PMS-HL的蛋白靶点,取其交集,筛选左慈丸治疗PMS-HL的潜在治疗靶点,构建“药物-活性成分-靶点”相互作用网络图。利用String数据库的蛋白相互作用分析功能筛选核心靶点。采用Metascape数据库对蛋白的功能及其通路进行富集分析。使用Autodock和Pymol对核心蛋白进行分子对接,确定核心靶点与左慈丸的关键活性成分之间的结合能力。于2022年9月—2023年1月建立绝经大鼠模型:假手术组(SHAM)组、去卵巢组(OVX)组、左慈丸(ZCW)组,并检测血清中关键蛋白白介素1β(IL-1β)水平,使用SPSS26.0进行统计分析。结果左慈丸组方中化合物的活性成分90个,潜在蛋白靶点226个,PMS-HL相关靶点2481个,左慈丸与PMS-HL交集靶点150个。基因本体论(GO)功能中获得生物过程共183个条目,分子功能103个条目,细胞成分103个条目;京都基因和基因组百科全书(KEGG)前三位分别是癌症通路、脂质与动脉粥样硬化病变通路和化学致癌的受体激活通路。分子对接显示,左慈丸治疗PMS-HL的主要活性成分有槲皮素、山柰酚、豆甾醇、β-谷甾醇、异鼠李素、薯蓣皂苷、四氢鸭脚木碱和海风藤酮;左慈丸的活性成分与核心靶蛋白:丝氨酸/苏氨酸蛋白激酶1(AKT1)、细胞肿瘤抗原p53(TP53)、白介素6(IL-6)、血管内皮生长因子(VEGFA)、胱天蛋白酶3(CASP3)、IL-1β、表皮生长因子受体(EGFR)、雌激素受体1(ESR1)结合能�Background In recent years,the symptoms of perimenopausal hearing loss(PMS-HL)have received widespread attention,but there is no targeted treatment.Zuoci pill has been used clinically for a hundred years,but there is no relevant research on the treatment of PMS-HL with this drug.Objective To explore the mechanism and therapeutic targets of Zuoci pill on PMS-HL through further validation of animal experiments based on the network pharmacology and molecular docking technology.Methods The active components and action targets of Zuoci pill were obtained through TCMSP and Uniprot databases,and the protein targets of PMS-HL were obtained through GeneCards,OMIM,TTD,DrugBank,and PharmGKB databases according to the composition of Zuoci pill from inception to February 2023,the intersection was taken to screen the potential therapeutic targets of Zuoci pill for the treatment of PMS-HL,and the"drug-active ingredient-target"interaction network diagram was constructed.The protein interaction analysis function of the String database was utilized to screen core targets.The Metascape database was used for enrichment analysis of the function of the proteins and pathways.Molecular docking of the core proteins was performed using Autodock and Pymol software to determine the binding capacity between key active ingredients and core targets.The menopausal animal model was established from September 2022 to January 2023,including Sham operation group(SHAM)group,ovariectomized(OVX)group,and Zuoci pill(ZCW)group,and serum level of the key protein interleukin 1β(IL-1β)was detected and statistically analyzed using SPSS 26.0.Results There were 90 active components,226 potential protein targets,2481 PMS-HL related targets,and 150 Zuoci pill and PMS-HL intersection targets for the compounds in the Zuoci pill formula.A total of 183 items for biological process,103 items for molecular function,and 103 items for cellular components were obtained in the Gene Ontology(GO)function.The top three Kyoto Encyclopedia of Genes and Genomes(KEGG)were can

关 键 词：围绝经期 听力损失 左慈丸 中药化学成分 网络药理学 分子对接 

分 类 号：R711.51[医药卫生—妇产科学] R764.43[医药卫生—临床医学]