| 1,171 | 10 | 52 |
| 下载次数 | 被引频次 | 阅读次数 |
目的：利用网络药理学方法并结合实验研究，深入探究麦门冬汤对特发性肺纤维化的治疗作用及其机制。方法：采用中药系统药理学数据库TCMSP、中国传统医学百科全书ETCM和SwissADME筛选并确定麦门冬汤中的活性成分。接着利用PubChem、SwissTargetPrediction和Uniport数据库挑选出中药活性成分的潜在作用靶标。借助GeneCards和OMIM数据库获取特发性肺纤维化的靶点基因。Venn diagrams绘图工具筛选出中药与疾病的交集靶点，利用Cytoscape3.9.1软件构建“中药-活性成分-疾病-靶点”网络关系图，并通过CytoNCA插件构建蛋白质相互作用网络，筛选得到核心靶点蛋白。运用DAVID进行GO及KEGG通路富集分析。最后使用博来霉素建立SD大鼠肺纤维化模型，观察大鼠肺组织肉眼标本及病理切片，并对其进行实时荧光定量PCR分析，比较治疗组与对照组TGF-β1、α-SMA、IL-4、IFN-γ、LC3-Ⅱ、beclin1的mRNA表达水平。结果：本研究共筛选得到麦门冬汤治疗IPF的作用靶点402个，其中核心靶点50个，对应5种中药的159种有效成分。GO富集分析和KEGG富集分析涉及PI3K-AKT信号通路、MAPK信号通路等信号通路治疗特发性肺纤维化。动物实验结果显示，与模型对照组相比，麦门冬汤治疗组可显著下调TGF-β1、α-SMA、IL-4 mRNA的相对表达水平（P<0.05），显著上调LC3-Ⅱ、beclin1、IFN-γmRNA的相对表达水平（P<0.05）。结论：本研究提示，麦门冬汤中关键活性成分可能在细胞自噬、炎症反应、巨噬细胞极化等生物过程方面发挥作用，发挥改善肺纤维化的作用。
Abstract：Objective: To investigate the therapeutic effect and mechanism of Maimendong decoction on idiopathic pulmonary fibrosis by utilizing network pharmacology methods and combining experimental research.Methods: TCMSP, ETCM and Swiss ADME were used to screen the active ingredients of Maimendong decoction. Through PubChem, SwissTargetPrediction and Uniport databases, the action targets of various components of traditional Chinese medicine were screened. The GeneCards database and OMIN database were applied to obtain target genes of idiopathic pulmonary fibrosis. Venn diagrams drawing tool was used to screen the intersection targets of traditional Chinese medicine and diseases. The "traditional Chinese medicine active ingredient disease target" network diagram was constructed by using the Cytoscape 3.9.1 software, and the protein interaction network(PPI) was constructed by using the CytoNCA plug-in to screen the core target proteins. DAVID was used for enrichment analysis of GO and KEGG pathways. Finally, we used bleomycin to establish a pulmonary fibrosis model in SD rats, observed the macroscopic specimens and pathological sections of rat lung tissue, and conducted real-time fluorescence quantitative PCR analysis to compare the mRNA expression levels of TGF-β1, α-SMA, IL-4, IFN-γ, LC3-Ⅱ, and beclin1 between the treatment group and the control group. Results:A total of 402 therapeutic targets of Maimendong decoction for IPF were screened, including 50 core targets, corresponding to 159 active ingredients of 5 traditional Chinese medicines. GO enrichment analysis and KEGG enrichment analysis involved the PI3K-AKT signal pathway, MAPK signal pathway and other signal pathways to treat idiopathic pulmonary fibrosis.The animal experiment results showed that compared with the model group,the Maimendong decoction group could significantly reduce the relative expression level of TGF-β1, α-SMA and IL-4 mRNA(P<0.05), significantly upregulated the relative expression level of mRNA LC3-Ⅱ, beclin1, IFN-γ(P<0.05).Conclusion: This study suggests that the key active components of Maimendong decoction may play a role in biological processes such as autophagy, inflammatory reaction, macrophage polarization, and improve pulmonary fibrosis.
1 Mortimer KM, Bartels DB, Hartmann N, et al. Characterizing health outcomes in idiopathic pulmonary fibrosis using US health claims data[J]. Respiration, 2020,99(2):108-118.
2 Maher TM, Bendstrup E, Dron L, et al. Global incidence and prevalence of idiopathic pulmonary fibrosis[J].Respir Res, 2021,22(1):197.
3 Mei Q, Liu Z, Zuo H,et al. Idiopathic pulmonary fibrosis:An update on pathogenesis[J]. Front Pharmacol,2022,12(1):797292.
4 Liu YM, Nepali K, Liou JP. Idiopathic pulmonary fibrosis:Current status, recent progress, and emerging targets[J]. J Med Chem, 2017,60(2):527-553.
5 Nwafor EO, Lu P, Liu Y, et al. Active components from traditional herbal medicine for the potential therapeutics of idiopathic pulmonary fibrosis:A systemic review[J]. Am J Chin Med, 2021,49(5):1093-1114.
6 Guo S, Song Y, Feng J, et al. Effects of Qizhukangxian granules on idiopathic pulmonary fibrosis:A randomized,double blind, placebo-controlled and multicenter clinical pilot trial[J]. J Tradit Chin Med, 2020,40(4):674-682.
7 Yu Y, Sun Z, Shi L, et al. Effects of feiwei granules in the treatment of idiopathic pulmonary fibrosis:A randomized and placebo-controlled trial[J]. J Tradit Chin Med, 2016,36(4):427-433.
8 黄云鉴，龚婕宁.论肺痹肺痿与肺纤维化的证治规律[J].时珍国医国药，2016,27(6):1439-1441.
9 白文梅，王兵，廖春燕.麦门冬汤对特发性肺纤维化患者一氧化碳弥散量、血清HA水平及中医证候积分的影响[J].四川中医，2019,37(8):92-95.
10 任娟宁，范文京，李彤，等.麦门冬汤化学成分及治疗肺纤维化研究进展[J].辽宁中医药大学学报，2022,24(6):155-159.
11 Ru J, Li P, Wang J, et al. TCMSP:A database of systems pharmacology for drug discovery from herbal medicines[J]. J Cheminform,2014,6(1):13.
12 Consortium TU. UniProt:The universal protein knowledgebase in 2023[J]. Nucleic Acids Res, 2022, 51(D1):D523-D531.
13 Hamosh A, Amberger JS, Bocchini C, et al. Online mendelian inheritance in man(OMIM?)：Victor McKusick′s magnum opus[J]. Am J Med Genet A, 2021, 185(11):3259-3265.
14 Safran M, Rosen N, Twik M, et al. The genecards suite[J]. Pract Guide Life Sci Databases,2021:27-56.
15 Szklarczyk D, Gable AL, Lyon D, et al. STRING v11:Protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets[J]. Nucleic Acids Res, 2019, 47(D1):D607-D613.
16 Sherman BT, Hao M, Qiu J, et al. DAVID:A web server for functional enrichment analysis and functional annotation of gene lists(2021 update)[J] Nucleic Acids Res, 2022, 50(W1):W216-W221.
17 徐叔云.药理实验方法学[M].3版.北京：人民卫生出版社，2002:1937.
18 陈将，章小敏，叶爱菊，等.槲皮素抗肺纤维化的分子机制研究[J].中国中医药科技，2018,25(5):666-669.
19 许火龙，聂磊，李春玉，等.槲皮素抗纤维化机制的研究进展[J].微量元素与健康研究，2021,38(3):70-73.
20 Ren J, Lu Y, Qian Y,et al. Recent progress regarding kaempferol for the treatment of various diseases[J]. Exp Ther Med, 2019,18(4):2759-2776.
21 Zhan H, Huang F, Ma W, et al. Protective effect of ginsenoside Rg1 on bleomycin-Induced pulmonary fibrosis in rats:Involvement of Caveolin-1 and TGF-β1 signal pathway[J]. Biol Pharm Bull, 2016,39(8):1284-1292.
22 Yang L, Chen PP, Luo M, et al. Inhibitory effects of total ginsenoside on bleomycin-induced pulmonary fibrosis in mice[J]. Biomed Pharm, 2019,114:108851.
23 王远敏，徐明兴，罗敏，等.基于网络药理学及实验验证初步探讨麦门冬汤治疗肺纤维化的作用机制[J].世界科学技术-中医药现代化，2022,24(10):3932-3940.
24 Ong CH, Tham CL, Harith HH, et al. TGF-β-induced fibrosis:A review on the underlying mechanism and potential therapeutic strategies[J]. Eur J Pharmacol, 2021,911:174510.
25 Hu HH, Chen DQ, Wang YN, et al. New insights into TGF-β/Smad signaling in tissue fibrosis[J]. Chem Biol Interact, 2018,292(8):76-83.
26 Gieseck RL, Wilson MS, Wynn TA. Type 2 immunity in tissue repair and fibrosis[J]. Nat Rev Immunol, 2018,18(1):62-76.
27 Cong LH, Li T, Wang H, et al. IL-17A-producing T cells exacerbate fine particulate matter-induced lung inflammation and fibrosis by inhibiting PI3K/Akt/mTOR-mediated autophagy[J]. J Cell Mol Med, 2020,24(15):8532-8544.
28 Liu MW, Su MX, Tang DY,et al. Ligustrazin increases lung cell autophagy and ameliorates paraquat-induced pulmonary fibrosis by inhibiting PI3K/Akt/mTOR and hedgehog signalling via increasing miR-193a expression[J]. BMC Pulm Med, 2019,19(1):35.
29 Yu JZ, Ying Y, Liu Y, et al. Antifibrotic action of Yifei Sanjie formula enhanced autophagy via PI3K-AKT-mTOR signaling pathway in mouse model of pulmonary fibrosis[J]. Biomed Pharmacother, 2019,118:109293.
30 Saito S, Zhuang Y, Shan B, et al. Tubastatin ameliorates pulmonary fibrosis by targeting the TGFβ-PI3K-Akt pathway[J]. PLoS One, 2017,12(10):e0186615.
31 Sui X, Kong N, Ye L, et al. p38 and JNK MAPK pathways control the balance of apoptosis and autophagy in response to chemotherapeutic agents[J]. Cancer Lett,2014,344(2):174-179.
32 Ye Z, Hu Y. TGF β1:Gentlemanly orchestrator in idiopathic pulmonary fibrosis(Review)[J]. Int J Mol Med,2021,48(1):132.
33 Suzuki K, Kirisako T, Kamada Y, et al. The pre-autophagosomal structure organized by concerted functions of APG genes is essential for autophagosome formation[J]. EMBO J, 2001,20(21):5971-5981.
34 Yue Z, Jin S, Yang C,et al. Beclin 1, an autophagy gene essential for early embryonic development, is a haploinsufficient tumor suppressor[J]. Proc Natl Acad Sci U SA, 2003,100(25):15077-15082.
35 Racanelli AC, Kikkers SA, Choi AMK,et al. Autophagy and inflammation in chronic respiratory disease[J].Autophagy,2018,14(2):221-232.
36 Patel AS, Lin L, Geyer A, et al. Autophagy in idiopathic pulmonary fibrosis[J]. PLoS One, 2012,7(7):e41394.
37 Wu MY, Lu JH. Autophagy and macrophage functions:Inflammatory response and phagocytosis[J]. Cells,2019,9(1):70.
38 Kishore A, Petrek M. Roles of macrophage polarization and macrophage-derived miRNAs in pulmonary fibrosis[J]. Front Immunol, 2021,12(8):678457.
39 Cosmi L, Maggi L, Santarlasci V,et al. T helper cells plasticity in inflammation[J]. Cytometry A, 2014,85(1):36-42.
40 Lee CM, Park JW, Cho WK, et al. Modifiers of TGF-β1effector function as novel therapeutic targets of pulmonary fibrosis[J]. Korean J Intern Med, 2014,29(3):281-290.
41 陈海红，王晓龙，王栋，等.麦门冬汤抗肺纤维化作用机制的网络药理学研究[J].山东中医药大学学报，2022,46(2):201-209.
42 Ghavami S, Yeganeh B, Zeki AA, et al. Autophagy and the unfolded protein response promote profibrotic effects of TGF-β in human lung fibroblasts[J]. Am J Physiol Lung Cell Mol Physiol, 2018,314(3):L493-L504.
43 Sosulski ML, Gongora R, Danchuk S,et al. Deregulation of selective autophagy during aging and pulmonary fibrosis:The role of TGFβ1[J]. Aging Cell, 2015,14(5):774-783.
基本信息:
DOI：10.13210/j.cnki.jhmu.20231129.002
中图分类号:R285
引用信息:
[1]马先,于明玥,周博文,等.基于网络药理学和实验验证探讨麦门冬汤治疗特发性肺纤维化的作用机制[J].海南医学院学报,2024,30(08):597-606.DOI:10.13210/j.cnki.jhmu.20231129.002.
基金信息:
齐鲁卫生与健康领军人才培育工程[鲁卫人才字（2020）3号]; 山东省自然科学基金面上项目（ZR2020MH353）; 2022年青年岐黄学者培养项目[国中医药人教函（2022）256号]; 山东省中医药高层次人才培育项目[鲁卫函（2023）143号]~~
2023-11-30
2023-11-30
2023-11-30