目的 探究清金益氣顆粒抗疲勞的作用及潛在作用機制。方法 通過中藥系統(tǒng)藥理學數(shù)據(jù)庫與分析平臺（TCMSP）、高通量中藥實驗和參考指南數(shù)據(jù)庫（HERB）、PubChem、Swiss Target Prediction等數(shù)據(jù)庫獲取藥物活性成分和作用靶點；通過GeneCards、OMIM數(shù)據(jù)庫收集疲勞的作用靶點；利用VENNY 2.1獲取藥物與疾病交集靶點，再聯(lián)合Cytoscape 3.9.1軟件構(gòu)建藥物-活性成分-疲勞交集靶點相互關(guān)系網(wǎng)絡(luò)；將交集靶點導入STRING數(shù)據(jù)庫構(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)庫對交集靶點進行基因本體（GO）和京都基因與基因組百科全書（KEGG）通路富集分析，預測清金益氣顆粒抗疲勞的作用機制；選取關(guān)鍵活性成分和核心靶點進行分子對接。通過負重力竭游泳實驗觀察小鼠負重力竭游泳時間；非負重游泳實驗測定小鼠血清乳酸（BLA）、尿素氮（BUN）、乳酸脫氫酶（LDH）、丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽過氧化物酶（GSH-Px）、肝糖原（LG）、肌糖原（MG）、葡萄糖（GLU）等指標評價清金益氣顆?？蛊谒幮?。結(jié)果 網(wǎng)絡(luò)藥理學和分子對接結(jié)果顯示清金益氣顆?？蛊诘?10個潛在作用靶點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）、缺氧誘導因子1（HIF-1）、叉頭框蛋白O（FoxO）等信號通路上，其主要活性成分和關(guān)鍵靶點蛋白結(jié)合能力較好。動物實驗結(jié)果表明，清金益氣顆粒可通過延長小鼠負重5%力竭游泳時間，降低非負重游泳小鼠血清中BLA、BUN、MDA水平，增加機體LG、MG、GLU水平儲存和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調(diào)節(jié)PI3K-AKT、MAPK、HIF-1、FoxO等信號通路影響機體能量代謝和氧化應激發(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

國家中醫(yī)藥管理局中醫(yī)藥創(chuàng)新團隊及人才支持計劃項目（ZYYCXTD-C-202203）