[關(guān)鍵詞]
[摘要]
目的 利用網(wǎng)絡(luò)藥理學(xué)方法對(duì)黃芪進(jìn)行多成分、多靶點(diǎn)研究,分析其在卒中相關(guān)性肌少癥中的作用靶點(diǎn)及相關(guān)通路。方法 采用TCMSP數(shù)據(jù)庫(kù)收集黃芪活性化合物并進(jìn)行初步篩選;采用Swiss Target Prediction數(shù)據(jù)庫(kù)預(yù)測(cè)活性化合物靶點(diǎn),通過GeneCards數(shù)據(jù)庫(kù)預(yù)測(cè)卒中相關(guān)性肌少癥作用靶點(diǎn),取兩者交集獲得交互靶點(diǎn)。采用String數(shù)據(jù)庫(kù)及Cytoscape軟件Network analyzer功能構(gòu)建共同靶點(diǎn)PPI網(wǎng)絡(luò)。采用DAVID數(shù)據(jù)庫(kù)并結(jié)合Cytoscape軟件對(duì)共同靶點(diǎn)進(jìn)行GO及KEGG富集分析。結(jié)果 收集篩選出黃芪20個(gè)活性化合物,616個(gè)作用靶點(diǎn),卒中相關(guān)性肌少癥136個(gè)作用靶點(diǎn),交集出25個(gè)交互靶點(diǎn),其中AKT1、IL-6、TNF、IGF1R、ESR1等蛋白相互作用最明顯,主要在細(xì)胞基質(zhì)中影響類固醇結(jié)合、鋅離子結(jié)合、蛋白質(zhì)絲氨酸/蘇氨酸激酶活性、雌激素受體活性、胰島素及能量代謝等生物過程,通過胰島素抵抗、HIF-1信號(hào)通路、TNF信號(hào)通路等在卒中相關(guān)性肌少癥中發(fā)揮作用,AKT1、PI3CG、mTOR、IL-6、TNF等交互靶點(diǎn)在各通路中參與次數(shù)較多。結(jié)論 黃芪在卒中相關(guān)性肌少癥中體現(xiàn)了多成分、多靶點(diǎn)、多途徑的特點(diǎn),其可能通過調(diào)控IRS-1/PI3K/AKT2/mTOR信號(hào)通路,靶向調(diào)控胰島素抵抗途徑相關(guān)能量代謝障礙,進(jìn)而治療和預(yù)防卒中相關(guān)性肌少癥。
[Key word]
[Abstract]
Objective To study the multi-components and multi-targets of Astragali Radix membranaceus by using the method of network pharmacology, and to analyze the targets and related pathways of Astragali Radix in stroke-related myosis. Methods The active compounds of Astragali Radix were collected by TCMSP database and screened. Swiss Target Prediction database was used to predict the target of active compounds, and GeneCards database was used to predict the target of stroke-related myosis. The common target PPI network is constructed by using String database and Cytoscape software Network analyzer function. DAVID database and Cytoscape software were used to analyze the enrichment of GO and KEGG. Results Tatolly 20 active compounds of Astragali Radix, 616 targets, 136 targets of stroke-related myosis were selected, and 25 interactive targets were intersected, among which AKT1, IL-6, TNF, IGF1R, ESR1 and other proteins had the most obvious interaction. It is mainly in the biological processes of steroid binding, zinc ion binding, protein serine/threonine kinase activity, estrogen receptor activity, insulin and energy metabolism in cell matrix. Insulin resistance, HIF-1 signaling pathway, TNF signaling pathway and other pathways play a role in stroke-related myosis. Conclusion Astragali Radix embodies the characteristics of multi-component, multi-target and multi-pathway in strokerelated myosis. It may target the treatment and prevention of stroke-related myosis by regulating the role of IRS-1/PI3K/AKT2/mTOR signaling pathway in energy reward disorder under the influence of insulin resistance pathway.
[中圖分類號(hào)]
R285.5
[基金項(xiàng)目]
國(guó)家自然科學(xué)基金面上項(xiàng)目(81874463);湖南省科技廳科技創(chuàng)新平臺(tái)與人才計(jì)劃(2017SK4005);湖南中醫(yī)藥大學(xué)研究生創(chuàng)新課題項(xiàng)目(2018CX07);湖南中醫(yī)藥大學(xué)中西醫(yī)結(jié)合一流學(xué)科開放基金項(xiàng)目(2018ZXYJH10)