目的 探究清金益氣顆?？蛊诘淖饔眉皾撛谧饔脵C(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)（TCMSP）、高通量中藥實(shí)驗(yàn)和參考指南數(shù)據(jù)庫(kù)（HERB）、PubChem、Swiss Target Prediction等數(shù)據(jù)庫(kù)獲取藥物活性成分和作用靶點(diǎn)；通過(guò)GeneCards、OMIM數(shù)據(jù)庫(kù)收集疲勞的作用靶點(diǎn)；利用VENNY 2.1獲取藥物與疾病交集靶點(diǎn)，再聯(lián)合Cytoscape 3.9.1軟件構(gòu)建藥物-活性成分-疲勞交集靶點(diǎn)相互關(guān)系網(wǎng)絡(luò)；將交集靶點(diǎn)導(dǎo)入STRING數(shù)據(jù)庫(kù)構(gòu)建蛋白質(zhì)-蛋白質(zhì)相互作用（PPI）網(wǎng)絡(luò)并利用DAVID數(shù)據(jù)庫(kù)對(duì)交集靶點(diǎn)進(jìn)行基因本體（GO）和京都基因與基因組百科全書(shū)（KEGG）通路富集分析，預(yù)測(cè)清金益氣顆?？蛊诘淖饔脵C(jī)制；選取關(guān)鍵活性成分和核心靶點(diǎn)進(jìn)行分子對(duì)接。通過(guò)負(fù)重力竭游泳實(shí)驗(yàn)觀察小鼠負(fù)重力竭游泳時(shí)間；非負(fù)重游泳實(shí)驗(yàn)測(cè)定小鼠血清乳酸（BLA）、尿素氮（BUN）、乳酸脫氫酶（LDH）、丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽過(guò)氧化物酶（GSH-Px）、肝糖原（LG）、肌糖原（MG）、葡萄糖（GLU）等指標(biāo)評(píng)價(jià)清金益氣顆粒抗疲勞藥效。結(jié)果 網(wǎng)絡(luò)藥理學(xué)和分子對(duì)接結(jié)果顯示清金益氣顆?？蛊诘?10個(gè)潛在作用靶點(diǎn)主要富集在磷脂酰肌醇3-激酶-蛋白激酶B（PI3K-AKT）、絲裂原活化蛋白激酶（MAPK）、缺氧誘導(dǎo)因子1（HIF-1）、叉頭框蛋白O（FoxO）等信號(hào)通路上，其主要活性成分和關(guān)鍵靶點(diǎn)蛋白結(jié)合能力較好。動(dòng)物實(shí)驗(yàn)結(jié)果表明，清金益氣顆?？赏ㄟ^(guò)延長(zhǎng)小鼠負(fù)重5%力竭游泳時(shí)間，降低非負(fù)重游泳小鼠血清中BLA、BUN、MDA水平，增加機(jī)體LG、MG、GLU水平儲(chǔ)存和LDH、SOD、GSH-Px活性發(fā)揮抗疲勞作用。結(jié)論 清金益氣顆粒可能通過(guò)調(diào)節(jié)PI3K-AKT、MAPK、HIF-1、FoxO等信號(hào)通路影響機(jī)體能量代謝和氧化應(yīng)激發(fā)揮抗疲勞的作用。

Objective To investigate the efficacy and potential mechanism of action of Qingjin Yiqi Granules against fatigue. Methods The active ingredients and targets of drug action were obtained through TCM Systematic Pharmacology Database and Analysis Platform (TCMSP), High-Throughput Experimental and Reference Guide Database for Traditional Chinese Medicines (HERB), PubChem, Swiss Target Prediction, and the disease-related targets of fatigue were collected through GeneCards and OMIM databases. VENNY 2.1 was used to obtain drug-disease intersection targets, and then the drug-active ingredient-fatigue-intersection target interrelationship network was constructed in conjunction with Cytoscape 3.9.1 software. The intersecting targets were imported into the STRING database to construct a protein-protein interaction (PPI) network and the intersecting targets were analyzed for gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment using the DAVID database, to predict the anti-fatigue mechanism of Qingjin Yixi Granules. Key active ingredients and core targets were selected for molecular docking. The mice were observed in the weight-bearing exhaustion swimming experiment, and the mice were measured in the non-weight-bearing swimming experiment for serum lactate (BLA), urea nitrogen (BUN), lactate dehydrogenase (LDH),malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), liver glycogen (LG), myoglobulin (MG), glucose (GLU), and so on. The efficacy of Qingjin Yiqi Granules against fatigue was evaluated. Results The results of network pharmacology and molecular docking showed that the 210 potential targets of anti-fatigue of Qingjin Yiqi Granules were mainly enriched in the signaling pathways such as PI3K-AKT, MAPK, HIF-1, FoxO, etc, and the binding ability of its main active ingredients and key target proteins was good. The results of animal experiments showed that Qingjin Yiqi Granules could exert antifatigue effects by prolonging the weight-bearing 5% exhaustion swimming time of mice, decreasing the serum content of BLA, BUN, and MDA in non-weight-bearing swimming mice, and increasing the body's LG, MG, and GLU content storage and the activities of LDH, SOD, and GSH-Px. Conclusions Qingjin Yiqi Granules may exert anti-fatigue effects by regulating the signaling pathways such as PI3K-AKT, MAPK, HIF-1, FoxO and other signaling pathways that affect the body's energy metabolism and oxidative stress.

R285.5

國(guó)家中醫(yī)藥管理局中醫(yī)藥創(chuàng)新團(tuán)隊(duì)及人才支持計(jì)劃項(xiàng)目（ZYYCXTD-C-202203）