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[1]張雪,徐彬,劉又文,等.基于網(wǎng)絡(luò)藥理學(xué)方法分析股骨頭壞死愈膠囊治療股骨頭壞死的潛在靶點(diǎn)及作用機(jī)制[J].中醫(yī)正骨,2022,34(01):1-7.
　ZHANG Xue,XU Bin,LIU Youwen,et al.Analysis of potential targets and mechanism of action of Gugutou Huaisiyu Capsule(股骨頭壞死愈膠囊)for treatment of osteonecrosis of femoral head using network pharmacology approach[J].The Journal of Traditional Chinese Orthopedics and Traumatology,2022,34(01):1-7.
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基于網(wǎng)絡(luò)藥理學(xué)方法分析股骨頭壞死愈膠囊治療股骨頭壞死的潛在靶點(diǎn)及作用機(jī)制()
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《中醫(yī)正骨》[ISSN:1001-6015/CN:41-1162/R]

卷:
第34卷
期數(shù):
2022年01期
頁(yè)碼:
1-7
欄目:
基礎(chǔ)研究
出版日期:
2022-01-20

文章信息/Info

Title:
Analysis of potential targets and mechanism of action of Gugutou Huaisiyu Capsule(股骨頭壞死愈膠囊)for treatment of osteonecrosis of femoral head using network pharmacology approach
作者:
張雪1; 徐彬2; 劉又文1; 李無(wú)陰1; 張虹1; 岳辰1
(1.河南省洛陽(yáng)正骨醫(yī)院/河南省骨科醫(yī)院,河南 洛陽(yáng) 471002; 2.浙江省立同德醫(yī)院,浙江 杭州 310012)
Author(s):
ZHANG Xue1; XU Bin2; LIU Youwen1; LI Wuyin1; ZHANG Hong1; YUE Chen1
1.Luoyang Orthopedic-Traumatological Hospital,Luoyang 471002,Henan,China;2.Tongde Hospital of Zhejiang Province,Hangzhou 310012,Zhejiang,China
關(guān)鍵詞:
股骨頭壞死;  股骨頭壞死愈膠囊;  網(wǎng)絡(luò)藥理學(xué);  靶點(diǎn);  藥物作用機(jī)制
Keywords:
femur head necrosis;  Gugutouhuaisiyu capsule;  network pharmacology;  target;  mechanism of drug action
摘要:
目的:分析股骨頭壞死愈膠囊治療股骨頭壞死(osteonecrosis of femoral head,ONFH)的潛在靶點(diǎn)及作用機(jī)制。方法:通過(guò)中藥系統(tǒng)藥理學(xué)數(shù)據(jù)庫(kù)與分析平臺(tái)(traditional Chinese medicine systems pharmacology database and analysis platform,TCMSP)和中醫(yī)藥百科全書(shū)(encyclopedia of traditional Chinese medicine,ETCM)數(shù)據(jù)庫(kù)檢索、篩選股骨頭壞死愈膠囊的有效成分和靶點(diǎn)。在GeneCards數(shù)據(jù)庫(kù)中檢索ONFH相關(guān)基因,從GEO數(shù)據(jù)庫(kù)下載包含ONFH基因數(shù)據(jù)的GSE74089數(shù)據(jù)集獲取ONFH差異表達(dá)基因,并通過(guò)與已獲取的股骨頭壞死愈膠囊藥物靶點(diǎn)基因取交集,篩選股骨頭壞死愈膠囊治療ONFH的關(guān)鍵靶點(diǎn)。利用Cytoscape軟件、STRING數(shù)據(jù)庫(kù)及已篩選出的股骨頭壞死愈膠囊有效成分和關(guān)鍵靶點(diǎn),構(gòu)建藥物-成分-靶點(diǎn)蛋白互作網(wǎng)絡(luò)。利用R軟件對(duì)篩選出的關(guān)鍵靶點(diǎn)基因進(jìn)行GO功能富集分析和KEGG通路富集分析,挖掘關(guān)鍵靶點(diǎn)的生物學(xué)功能和通路信息。利用Cytoscape軟件和STRING數(shù)據(jù)庫(kù)構(gòu)建關(guān)鍵靶點(diǎn)蛋白互作網(wǎng)絡(luò),篩選股骨頭壞死愈膠囊治療ONFH的核心靶點(diǎn)。結(jié)果:從TCMSP和ETCM數(shù)據(jù)庫(kù)中共篩選出股骨頭壞死愈膠囊的有效成分203個(gè)、靶點(diǎn)592個(gè)。在GeneCards數(shù)據(jù)庫(kù)中檢索到ONFH相關(guān)基因2033個(gè),在GEO數(shù)據(jù)庫(kù)GSE74089數(shù)據(jù)集獲得ONFH差異表達(dá)基因8178個(gè)。將ONFH相關(guān)基因、ONFH差異表達(dá)基因及藥物靶點(diǎn)基因取交集后,獲得股骨頭壞死愈膠囊治療ONFH的關(guān)鍵靶點(diǎn)57個(gè)。構(gòu)建的藥物-成分-靶點(diǎn)蛋白互作網(wǎng)路包含200個(gè)節(jié)點(diǎn)和500條邊,蛋白互作網(wǎng)絡(luò)顯示137個(gè)藥物有效成分與57個(gè)關(guān)鍵靶點(diǎn)有對(duì)應(yīng)關(guān)系。GO功能富集分析結(jié)果顯示,關(guān)鍵靶點(diǎn)的基因功能主要涉及激素反應(yīng)、氧供反應(yīng)、免疫系統(tǒng)過(guò)程調(diào)節(jié)、骨細(xì)胞調(diào)節(jié)、骨小梁形成、骨重塑調(diào)節(jié)、骨化調(diào)節(jié)、軟骨發(fā)育及骨合成過(guò)程等; KEGG信號(hào)通路富集分析結(jié)果顯示,關(guān)鍵靶點(diǎn)的主要信號(hào)通路包括缺氧誘導(dǎo)因子1(hypoxia-inducible factor 1,HIF-1)信號(hào)通路、核轉(zhuǎn)錄因子-κB(nuclear factor-κB,NF-κB)信號(hào)通路、鞘脂信號(hào)通路、p53信號(hào)通路、鈣信號(hào)通路、精氨酸和脯氨酸代謝信號(hào)通路。構(gòu)建的關(guān)鍵靶點(diǎn)蛋白互作網(wǎng)絡(luò)顯示,腫瘤壞死因子(tumor necrosis factor,TNF)為具有最高度值的關(guān)鍵靶點(diǎn),即核心靶點(diǎn)。結(jié)論:股骨頭壞死愈膠囊治療ONFH的潛在靶點(diǎn)為TNF,其作用機(jī)制可能為通過(guò)HIF-1、NF-κB、p53等信號(hào)通路,參與激素反應(yīng)、氧供反應(yīng)、免疫系統(tǒng)過(guò)程調(diào)節(jié)及骨形成調(diào)節(jié)等生物學(xué)過(guò)程。
Abstract:
Objective:To explore the potential targets and mechanism of action of Gugutou Huaisiyu Capsule(股骨頭壞死愈膠囊,GHC)in treatment of osteonecrosis of femoral head(ONFH).Methods:The active ingredients and action targets of GHC were screened by retrieving Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)and Encyclopedia of Traditional Chinese Medicine(ETCM).The ONFH-related genes were searched out from GeneCards database,and the ONFH-related differentially expressed genes(DEGs)were obtained from the microarray dataset GSE74089 downloaded from the Gene Expression Omnibus(GEO)database.The key targets of GHC for treatment of ONFH were selected through overlapping ONFH-related genes,ONFH-related DEGs with the obtained drug target genes of GHC.The drug-ingredient-target network was built by using Cytoscape software and STRING database based on the active ingredients and key targets of GHC.The GO function and KEGG pathway enrichment analysis were performed on key target genes respectively by using R software to dig biological functions and pathways of the key targets.The protein-protein interaction(PPI)network of the key targets was built by using Cytoscape software and STRING database for screening the core targets of GHC for treatment of ONFH.Results:Two hundred and three active ingredients and 592 targets of GHC were screened out from TCMSP and ETCM,and 2033 ONFH-related genes and 8178 ONFH-related DEGs were obtained from GeneCards and GEO database respectively.Fifty-seven key targets of GHC for treatment of ONFH were obtained through overlapping ONFH-related genes,ONFH-related DEGs with the drug target genes of GHC.The drug-ingredient-target network diagram consists of 200 nodes and 500 edges,and the PPI network illustrated the corresponding connections between 137 active ingredients and 57 key targets.The results of GO function enrichment analysis suggested that the key targets were mainly involved in the response to hormone,response to oxygen level,regulation of immune system process,regulation of osteocytes,bone trabecula morphogenesis,regulation of bone remodeling,regulation of ossification,cartilage development and osteogenesis.The results of KEGG signaling pathway enrichment analysis indicated that the key targets were mainly enriched in hypoxia-inducible factor 1(HIF-1),nuclear factor-κB(NF-κB),sphingolipid,p53,calcium,arginine and proline metabolism signaling pathways.The PPI network of the key targets demonstrated that the tumor necrosis factor(TNF)with the highest value acted as the core target.Conclusion:TNF is the potential target of GHC in treatment of ONFH.It may participate in the responses to hormones and oxygen level and the regulation of immune system process and ossification through the signaling pathways of HIF-1,NF-κB and p53.

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基金項(xiàng)目:國(guó)家自然科學(xué)基金項(xiàng)目(82074472,81804126)
通訊作者:劉又文 E-mail:[email protected]
更新日期/Last Update: 1900-01-01