摘要
目的筛选化瘀散结灌肠液治疗子宫内膜异位症的活性成分、活性成分靶基因,探讨靶基因的生物学功能及相关信号通路。方法依托TCMSP数据库及相关文献查询化瘀散结灌肠液包含15味中药成分所对应的靶基因,通过ADME参数(Caco-2≥0.4,DL>0.36,OB≥30%)筛选化瘀散结灌肠液可能的活性成分及其靶基因,并通过Uniport数据库进行名称规范;然后,运用Genecards数据库获取子宫内膜异位症的发病相关靶点;并利用R语言将化瘀散结灌肠液成分靶基因与子宫内膜症发病相关特异性靶基因交集,进而得到化瘀散结灌肠液及子宫内膜异位症共有潜在靶基因;并提交至STRING平台(置信度>0.9),获得蛋白互作网络,采用Cytoscape 3.7.2进行蛋白互作网络拓扑分析,并筛选重要靶点(Degree排序前十);最后,通过DAVID数据库进行潜在共有靶基因生物学功能分析(GO注释和KEGG富集)。结果治疗子宫内膜异位症的化瘀散结灌肠液中的15味中药涵盖了58个活性成分,活性成分包括β-谷甾醇、槲皮素、豆甾醇、菜油甾醇等,活性成分靶基因主要有PGR、NCOA2、PTCS2、SCN5A等。其中重要靶基因有STAT3、JUN、TP53等基因,生物功能主要涉及RNA聚合酶Ⅱ启动子转录的正调控、药物反应、凋亡过程的负调控等生物过程,细胞核、细胞质等重要的细胞组分,蛋白结合、酶结合、转录因子结合等分子功能;其富集在癌症、TNF、自噬等多条信号通路上。结论化瘀散结灌肠液治疗子宫内膜异位症的活性成分包括β-谷甾醇、槲皮素、豆甾醇、菜油甾醇等,活性成分靶基因主要有PGR、NCOA2、PTCS2、SCN5A等,化瘀散结灌肠液治疗子宫内膜异位症的重要靶点主要有STAT3、JUN、TP53等基因,其参与RNA聚合酶Ⅱ启动子转录的正调控、药物反应等生物学过程,相关通路主要有癌症、TNF、自噬等信号通路。
Objective of endometriosis,and to explore the biological functions and related information pathways of the target genes.Methods The target genes of Huayu Sanjie enema containing 15 traditional Chinese medicine components were searched in the TCMSP database and related literatures,and the possible active ingredients and target were screened out by ADME parameters(Caco-2≥0. 4,DL>0. 36,OB≥30%);then,Genecards database was used to obtain the disease-related targets of endometriosis;we used the R language to intersect the target genes of the components of Huayu Sanjie enema with the specific target genes related to the pathogenesis of endometriosis,and then obtained the potential target genes shared by Huayu Sanjie enema and endometriosis to submitted them to the STRING platform(confidence level> 0. 9);the protein-protein interaction network was obtained. Cytoscape 3. 7. 2 was used to analyze the protein interaction network topology,and we screened out the important targets;finally,the potential target genes shared by Huayu Sanjie enema and endometriosis were analyzed by using the DAVID database for biological function analysis(GO annotation and KEGG enrichment).Results A total of 1 583 ingredients were collected from Huayusanjie enema with 15 traditional Chinese medicines,and 58 active ingredients and 110 target genes were screened out by ADME,including β-sitosterol,quercetin,stigmasterol,campesterol,etc. Totally 1 446 endometriosis-related target genes,and 55 the potential target genes shared by Huayu Sanjie enema and endometriosis were screened out. The biological functions of 55 potential target genes were mainly involved in negative regulation of transcription from RNA polymerase II promoter and positive regulation of transcription from RNA polymerase II promoter,and were enriched in cancer signaling pathway,TNF signaling pathway,autophagy signaling pathways,etc.Conclusions with 15 herbs,and 55 the potential target genes shared by Huayu Sanjie enema and endometriosis are screened out. The55 potential target g
作者
徐信
宗春晓
邢玉
徐立
祝洁
薛晓鸥
XU Xin;ZONG Chunxiao;XING Yu;XU Li;ZHU Jie;XUE Xiaoou(Dongzhimen Hospital of Beijing University of Chinese Medicine,Beijing 100700,China)
出处
《山东医药》
CAS
2021年第15期10-14,共5页
Shandong Medical Journal
基金
G20工程支撑保障项目(Z151100003815014)
国家自然科学青年基金赞助项目(81904241)。
