宫外孕2号方“异病同治”异位妊娠和子宫内膜异位症-慢性盆腔痛的机制研究

Mechanism of No.2 Formula of Ectopic Pregnancy for“Homotherapy for Heteropathy”in the Treatment of Ectopic Pregnancy and Endometriosis-Chronic Pelvic Pain

目的:探讨宫外孕2号方“异病同治”异位妊娠和子宫内膜异位症-慢性盆腔痛的作用机制。方法:通过查找文献、数据库检索宫外孕2号方中5味中药相关的所有化学成分和作用靶点。对异位妊娠、子宫内膜异位症-慢性盆腔痛共有靶点进行基因本体(GO)分析、京都基因与基因组百科全书(KEGG)分析和模块分析。采用STRING数据库制作靶点的蛋白质-蛋白质相互作用网络,并进行分子对接验证。运用bioGPS、GeneCards和DisGeNET数据库分别检索关键靶点的器官组织分布、亚细胞分布和蛋白归属。结果:通过中药与疾病取交集后获得共同靶点85个,筛选关键靶点32个,主要涉及蛋白激酶B(Akt)1、基质金属蛋白酶(MMP)2、MMP9和丝裂原激活的蛋白激酶1等。GO分析的类固醇激素水平、炎症反应和细胞凋亡,KEGG分析的癌症通路、磷脂酰肌醇3激酶-Akt信号通路、内分泌抵抗通路、缺氧诱导因子1信号通路、核因子κB信号通路和血管内皮生长因子信号通路,均对宫外孕2号方“异病同治”异位妊娠和子宫内膜异位症-慢性盆腔痛起重要作用。结论:宫外孕2号方治疗异位妊娠和子宫内膜异位症-慢性盆腔痛的共同机制主要与调节内分泌、神经和免疫因素有关,与干预癌症通路有一定相关性。

OBJECTIVE:To probe into the mechanism of No.2 Formula of Ectopic Pregnancy for“homotherapy for heteropathy”in the treatment of ectopic pregnancy and endometriosis-chronic pelvic pain.METHODS:All the chemical components and action targets related to 5 flavors of traditional Chinese medicine in No.2 Formula of Ectopic Pregnancy were retrieved by literature and database retrieval.The Gene Ontology(GO)analysis,Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis and modular analysis were performed on common targets of ectopic pregnancy and endometriosis-chronic pelvic pain.The protein-protein interaction networks of the targets were produced by using STRING and validated by molecular docking.The organ tissue distribution,subcellular distribution and protein attribution of key targets were retrieved by using bioGPS,GeneCards and DisGeNET databases,respectively.RESULTS:A total of 85 common targets were obtained through the intersection of traditional Chinese medicine and diseases,32 key targets were screened out,mainly involving protein kinase B(Akt)1,matrix metalloproteinase(MMP)2,MMP9,mitogen-activated protein kinase 1,etc.The steroid hormone levels,inflammatory response and apoptosis in GO analysis,the cancer pathway,phosphatidylinositol 3-kinase-Akt signaling pathway,endocrine resistance pathway,hypoxia-inducible factor 1 signaling pathway,nuclear factor κB signaling pathway and vascular endothelial growth factor signaling pathway in KEGG analysis were playing important roles in the treatment of ectopic pregnancy and endometriosis-chronic pelvic pain with No.2 Formula of Ectopic Pregnancy.CONCLUSIONS:The mechanism of No.2 Formula of Ectopic Pregnancy in the treatment of ectopic pregnancy and endometriosis-chronic pelvic pain is mainly related to the regulation of endocrine,neurological and immunological factors,which also has some relevance to the intervention of cancer pathways.