从细胞焦亡角度挖掘治疗湿热蕴结型盆腔炎性疾病后遗症的天然药物成分

Exploration of Natural Pharmaceutical Components for Sequelae of Pelvic Inflammatory Disease of Damp-Heat Accumulation Type from the Perspective of Pyroptosis

目的:通过生物信息学及分子对接技术,从细胞焦亡角度挖掘得到治疗湿热蕴结型盆腔炎性疾病后遗症(SPID)的天然药物成分,为湿热蕴结型SPID的治疗及新药的研发开拓新思路。方法:通过GEO数据库检索与SPID相关的符合筛选条件的数据集,归纳整理后对其进行limma差异分析获得SPID的差异表达靶点。通过GeneCards平台,以湿热蕴结型SPID的主症及次症为关键词进行检索,获得湿热蕴结型的靶点。通过中国知网、万方数据库和PubMed寻找细胞焦亡相关的靶点,三者合并取交集得到与细胞焦亡相关的湿热蕴结型SPID靶点。利用CMap平台对获得的靶点进行计算分析得到天然药物小分子,并通过中药系统药理学数据库与分析平台寻找天然药物小分子所来源的天然药物,最后进行分子对接验证。结果:从GEO数据库筛选出GSE165004数据集,通过limma差异分析得到3073个靶点。收集得到与细胞焦亡相关靶点33个。细胞焦亡、SPID差异表达靶点及其湿热蕴结型靶点合并取交集得到4个靶点,为白细胞介素18、半胱氨酸蛋白酶9、半胱氨酸蛋白酶5和NOD样受体热蛋白结构域相关蛋白3。CMap数据库结果显示,喜树碱、小檗碱、玫瑰树碱、金合欢素和芹菜素等天然药物小分子化合物具有较高的负相关,并能与分析获得的靶点形成良好的分子对接。结论:通过生物信息学及分子对接结果,来源于败酱草等天然药物的金合欢素、芹菜素等可能成为治疗湿热蕴结型SPID的关键候选天然药物小分子,为SPID的治疗药物研究开辟了新方向,也为新药的研制开发提供了一定借鉴。

OBJECTIVE:To explore the natural pharmaceutical components for the treatment of sequelae of pelvic inflammatory disease(SPID)of damp-heat accumulation type from the perspective of cell pyroptosis through bioinformatics and molecular docking technology,so as to probe into new ideas for the treatment of SPID of damp-heat accumulation type and research and development of new drugs.METHODS:Data related to SPID that met the screening conditions was retrieved through GEO database,and differential expression targets of SPID were obtained by limma differential analysis after summarization.Through the GeneCards platform,the main and secondary symptoms of SPID of damp-heat accumulation type were searched as keywords,and the targets of damp-heat accumulation type were obtained.CNKI,Wanfang Data and PubMed were used to find targets related to cell pyroptosis.The three were combined and intersected to obtain targets for SPID of damp-heat accumulation type associated with cell pyroptosis.CMap platform was used to calculate and analyze the obtained targets to obtain natural drug small molecules,and the natural drugs derived from natural drug small molecules were found through Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,and finally the molecular docking verification was carried out.RESULTS:GSE165004 dataset was screened out from GEO database,and 3073 targets were obtained after limma differential analysis.A total of 33 targets related to pyroptosis were collected.Four targets were obtained by combining and intersecting the cell pyroptosis and differential expression targets for SPID of damp-heat accumulation type,namely interleukin 18(IL-18),CASP9,CASP5 and NLRP3.Results of CMap database showed that small molecule compounds of natural medicines such as Camptothecin,berberine,ellipticine,Acacetin and Apigenin had high negative correlation and could form good molecular docking with the targets obtained by analysis.CONCLUSIONS:Through the results of bioinformatics and molecular docking,Acacetin and Apigenin may become the key small molecules of natural medicines for the treatment of SPID of damp-heat accumulation type,which opens up a new direction for the research of SPID medicines and provides some reference for the research and development of new drugs.