目的 基于網(wǎng)絡(luò)藥理學和體內(nèi)實驗探討抗衰老片抗衰老的作用機制。方法 利用中藥系統(tǒng)藥理學數(shù)據(jù)庫與分析平臺（TCMSP）篩選抗衰老片中組方藥材的主要化學成分及其靶點，并通過文獻檢索、Pubchem對抗衰老片中藥材的主要成分進行補充，經(jīng)SwissTargetPrediction數(shù)據(jù)庫預(yù)測靶點；通過GeneCards、OMIM數(shù)據(jù)庫獲取衰老相關(guān)靶點；通過Venny2.1.0平臺獲得抗衰老片成分與衰老的共同靶點；基于STRING數(shù)據(jù)庫和Cytoscape 3.8.0軟件構(gòu)建藥物與疾病共同靶點的蛋白質(zhì)相互作用網(wǎng)絡(luò)（PPI）；基于R語言進行基因本體（GO）生物功能分析和京都基因與基因組百科全書（KEGG）通路富集分析。以秀麗隱桿線蟲為實驗對象，觀察抗衰老片對N2野生型秀麗隱桿線蟲壽命及百草枯誘導的N2野生型線蟲及突變體CB1370、CF1038、MQ1333、MQ887、TJ1052壽命的影響，探究抗衰老片抗衰老的作用及潛在的作用機制。結(jié)果 篩選出抗衰老片221個活性成分和1 232個預(yù)測靶點，衰老相關(guān)靶點12 081個，抗衰老片成分和疾病的共同靶點1 020個。KEGG富集分析結(jié)果主要涉及磷脂酰肌醇-3-激酶/蛋白激酶B（PI3K/Akt）信號通路、晚期糖基化終末產(chǎn)物/晚期糖基化終末產(chǎn)物受體（AGE/RAGE）信號通路、絲裂原活化蛋白激酶（MAPK）信號通路等。線蟲實驗結(jié)果表明，抗衰老片可延長正常情況下及百草枯誘導下的N2野生型秀麗隱桿線蟲的壽命，提高秀麗隱桿線蟲對百草枯的耐性；與相應(yīng)各對照組相比，抗衰老片無法延長突變體TJ1052和CF1038在氧化應(yīng)激下的壽命，但突變體CB1370、MQ1333和MQ887在氧化應(yīng)激下的壽命可被延長。結(jié)論 抗衰老片對秀麗隱桿線蟲具有延長壽命的作用，其潛在的機制可能依賴于PI3K信號通路和叉頭轉(zhuǎn)錄因子（FOXO）信號通路，而不依賴于胰島素受體信號通路和線粒體相關(guān)信號通路。

Objective To explore the anti-aging mechanism of Kangshuailao Tablet (KSLT) based on network pharmacology and in vivo experiments. Methods Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to screen the main chemical components and their targets of Chinese materia medica in KSLT and the major components of Chinese materia medica in KSLT were supplemented by literature and Pubchem, and the targets of supplemented components were predicted by the SwissTargetPrediction. Aging-related targets were obtained from the database of GeneCards and OMIM. Common targets of KSLT and aging were got by Venny2.1.0. The protein-protein interaction (PPI) network of the common targets of drugs and diseases was constructed based on the STRING and Cytoscape 3.8.0 software. Gene ontology (GO) function enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis were carried out based on R language. To explore the anti-aging effect and potential mechanism of KSLP, N2 wild-type Caenorhabditis elegans (C. elegans) were performed to observe the anti-aging effect of KSLT on the life span, and the potential anti-aging mechanism of KSLT was investigated by paraquat-induced N2 wild-type C. elegans and mutants CB1370, CF1038, MQ1333, MQ887 and TJ1052. Results There were 221 active ingredients, 1 232 predicted targets in KSLT, 12 081 targets in aging-related targets, and 1 020 common targets of KSLT and aging. The selected signaling pathways of KEGG pathway analysis mainly included phosphatidylinositol 3- kinase and protein kinase B (PI3K/Akt) signaling pathway, advanced glycation end products/receptor for advanced glycation end products (AGE/RAGE) signaling pathway, mitogen-activated protein kinase (MAPK) signaling pathway, etc. The experimental results showed that KSLT prolonged the lifespan of C. elegans and improved the tolerance of C. elegans to paraquat. Compared with the corresponding control groups, KSLT was unable to extend the lifespan of mutants TJ1052 and CF1038 under oxidative stress, but the lifespan of mutants CB1370, MQ1333, and MQ887 was prolonged by KSLT under oxidative stress. Conclusion KSLTP had anti-aging effects on C. elegans, and the underlying might depend on PI3K and forkhead box protein O (FOXO) signaling pathways, but not on insulin receptors signaling pathway and mitochondria-related signaling pathways.

R285.5

上海市科委專項“上海醫(yī)藥戰(zhàn)略大品種二次開發(fā)”（15DZ1900100）