“下法”结合生信探讨中药结肠透析方治疗CKD的作用机制  

Study on Mechanism of TCM Colon Dialysis Prescription in Treatment of CKD Based on Purgative Method and Bioinformatics

作　　者：向雪芹 赵菁莉[1] 赵晰[1] XIANG Xueqin;ZHAO Jingli;ZHAO Xi(Tianjin University of Chinese Medicine,The First Affiliated Hospital of Tianjin University of Chinese Medicine,Tianjin 30011l,China)

机构地区：[1]天津中医药大学第一附属医院国家中医针灸临床医学研究中心,天津300111

出　　处：《实用中医内科杂志》2023年第8期50-56,I0009-I0011,共10页Journal of Practical Traditional Chinese Internal Medicine

基　　金：国家自然科学基金资助项目(81603544)。

摘　　要：目的 探究天津中医药大学第一附属医院中药结肠透析方(大黄、牡蛎、蒲公英)治疗慢性肾脏病(CKD)的作用机制。方法 使用BATMAN-TCM收集大黄、牡蛎、蒲公英三味中药的化学成分和相关靶点,在DisGeNet、DrugBank等数据库检索CKD疾病靶点。选用Venny数据库获取药物-疾病交集靶点后,将其导入STRING数据库并利用Cytoscape 3.9.1软件进行可视化;在DAVID数据库对交集靶点进行GO功能和KEGG富集分析;最后运用Pymol、AutoDock等软件进行分子对接验证。结果 得到234个药物-疾病交集靶点,其中MAPK1、AKT1、PIK3R1等18个靶点为核心靶点,GO富集分析得到770个结果(P<0.01,FDR<0.05),包括610条生物过程,65条细胞组成,95条分子功能,其主要作用于质膜、细胞质、胞质等功能位置。KEGG富集分析主要涉及炎性反应、免疫抑制、糖脂代谢等,其中与PI3K-Akt信号通路联系最为紧密。分子对接结果显示核心靶点与活性成分结合稳定,靶点AKT1与黄体酮的结合能最高(-10.759)。结论 研究初步验证了中医结肠透析治疗慢性肾脏病具有“多途径、多通路、多靶点”的特点,以期为更深层次的实验研究和临床诊疗提供思路。Objective To explore the mechanism of traditional Chinese medicine colon dialysis prescription[Dahuang(rhubarb),Muli(oyster),Pugongying(dandelion)] in the treatment of chronic kidney disease(CKD).Methods The chemical components and related targets of Dahuang(rhubarb),Muli(oyster),Pugongying(dandelion)were collected using Batch-TCM,and the targets of CKD disease were searched in DisGeNet and DrugBank databases.Venny database was selected to obtain drug-disease intersection targets,which were imported into STRING database and visualized by Cytoscape 3.9.1 software.GO function and KEGG enrichment analysis were performed on the intersection targets in DAVID database.Finally,Pymol,AutoDock and other software were used for molecular docking verification.Results A total of 234 drug-disease intersection targets were obtained,including 18 targets such as MAPK1,AKT1 and PIK3R1 as core targets,770 results were obtained by GO enrichment analysis(P<0.01,FDR<0.05),including 610 biological processes,65 cell composition and 95 molecular functions.It mainly acted on functional sites such as plasma membrane,cytoplasm and cytoplasm.KEGG enrichment analysis mainly involves inflammatory response,immunosuppression,glucose and lipid metabolism,among which the PI3K-Akt signaling pathway was most closely related.Molecular docking results showed that the core target was stable in binding to the active ingredient and AKT1 had the highest binding energy with progesterone(-10.759).Conclusion This study preliminarily verified the characteristics of"multi-pathway,multi-pathway and multi-target"in the treatment of chronic kidney disease by traditional Chinese medicine colonic dialysis prescription,in order to provide ideas for further experimental research and clinical diagnosis and treatment.

关 键 词：慢性肾脏病 中药结肠透析 下法 生物信息学 分子对接 

分 类 号：R285.5[医药卫生—中药学]