[關(guān)鍵詞]
[摘要]
目的 通過網(wǎng)絡藥理學探討黃連溫膽湯治療心律失常的機制。方法 通過TCMSP平臺收集黃連溫膽湯相關(guān)藥物的有效成分及作用靶點;經(jīng)過UniProt獲取標準蛋白名并轉(zhuǎn)換靶點基因名;使用DIGSEE、OMIN、Drugbank等數(shù)據(jù)庫收集心律失常疾病基因靶點,合并后去重與復方中藥靶點取交集;使用String數(shù)據(jù)庫繪制蛋白相互作用(PPI)網(wǎng)絡,使用Cytoscape 3.9.1經(jīng)過拓撲分析獲取核心靶點;使用R語言進行京都基因與基因組百科全書(KEGG)及基因本體(GO)富集分析并對排名靠前的通路進行可視化處理;對KEGG排名靠前的通路使用Cytoscape 3.9.1構(gòu)建中藥成分–靶點–通路圖。結(jié)果 通過拓撲分析得到表皮生長因子受體(EGFR)、絲裂原活化蛋白激酶(MAPK)1、MAPK3、信號轉(zhuǎn)導和轉(zhuǎn)錄激活因子3(STAT3)、CAMP反應性元素結(jié)合蛋白1(CREB1)、雌激素受體(ESR1)等19個核心靶點;通過KEGG富集分析共得到186條信號通路,黃連溫膽湯可能通過晚期搪基化終產(chǎn)物及其受體(AGE-RAGE)、磷脂酰肌醇3-激酶(phosphatidylinositol-3-kinase,PI3K)/蛋白激酶B(protein kinase B,Akt)、MAPK等信號通路對心律失常起治療作用。結(jié)論 黃連溫膽湯可通過多種目標基因、分子通路治療心律失常。
[Key word]
[Abstract]
Objective To explore the mechanism of Huanglian Wendan Decoction in treatment of arrhythmia based on network pharmacology. Methods The effective components and targets of Huanglian Wendan Decoction were collected by TCMSP platform. The standard protein name was obtained by UniProt and the target gene name was converted. The gene targets of arrhythmia were collected by DIGSEE, OMIN, Drugbank, and other databases. PPI protein interaction network was drawn using String database, and the core target was obtained using Cytoscape 3.9.1 through topological analysis. KEGG and GO enrichment analysis was performed using R language, and the top-ranked pathways were visualized. Cytoscape 3.9.1 was used to construct TCM component-target-pathway map for pathways with high KEGG ranking. Results 19 Core targets including EGFR, MAPK1, MAPK3, STAT3, CREB1, and ESR1 were obtained. A total of 186 signaling pathways were obtained through KEGG enrichment analysis. Huanglian Wendan Decoction may have therapeutic effects on arrhythmia through AGE-RAGE, PI3K-Akt, and MAPK and other signaling pathways. Conclusion Huanglian Wendan Decoction can treat arrhythmia through multiple target gene and molecular pathways.
[中圖分類號]
R972
[基金項目]
江西省自然科學基金資助項目(20202BABL206141);國家自然科學基金項目(81960820);全國中醫(yī)藥創(chuàng)新骨干人才[國中醫(yī)藥人教函(2019)128號];江西省中醫(yī)藥中青年骨干人才[贛中醫(yī)藥科教字[2020]2號]