LI Quan-yao,YAO Li-qiu,WANG Xiao,et al.Study on the Mechanism of Longteng Tongluo Prescription for the Treatment of Chemotherapy-induced Peripheral Neuropathy Based on Network Pharmacology[J].Chinese Journal of Library and Information Science for Traditional Chinese Medicine,2022,46(2):1-8.[doi:10.3969/j.issn.2095-5707.2022.02.001]
基于网络药理学研究龙藤通络方治疗化疗致周围神经病变的作用机制
- Title:
- Study on the Mechanism of Longteng Tongluo Prescription for the Treatment of Chemotherapy-induced Peripheral Neuropathy Based on Network Pharmacology
- 文章编号:
- 2095-5707(2022)02-0001-08
- Keywords:
- Longteng Tongluo Prescription; chemotherapy-induced peripheral neuropathy; network pharmacology; mechanism
- 分类号:
- R277.7；R273
- 文献标志码:
- A
- 摘要:
- 目的 运用网络药理学探讨龙藤通络方治疗化疗致周围神经病变（Chemotherapy-induced Peripheral Neuropathy，CIPN）的作用机制。方法 运用TCMSP和UniProt数据库获取药物的活性成分和作用靶点，借助人类基因数据库（GeneCards）、在线人类孟德尔遗传数据库（OMIM）、TTD、DisGeNET及DrugBank数据库，以“chemotherapy-induced peripheral neuropathy”为关键词检索疾病相关靶点，药物作用靶点与疾病靶点取交集得到龙藤通络方作用于CIPN的预测靶点，采用Cytoscape 3.7.1软件构建龙藤通络方活性成分-靶点可视化网络、龙藤通络方与CIPN共同靶点网络。利用STRING数据库和Cytoscape 3.7.1软件构建蛋白相互作用网络，并进行网络拓扑学分析。采用Metescape数据库和在线作图工具平台进行GO功能和KEGG通路富集分析。结果 共筛选出龙藤通络方71个活性成分，183个靶点基因；疾病相关靶点基因582个；获得91个药物与疾病共同靶点基因，核心靶点涉及AKT1、TP53、ALB、VEGFA、JUN、IL-6、CASP3、TNF、STAT3、PTEN、MYC、IL-1β、EGF、HIF1A、ESR1、EGFR等。GO功能分析得出1 520个生物过程、69个细胞组成、133个分子功能。KEGG通路分析发现190条相关信号通路，主要富集于癌症通路、癌症蛋白聚糖、小细胞肺癌、血管内皮生长因子信号通路、NF-КB信号通路、甲状腺癌等与CIPN相关的通路。结论 龙藤通络方治疗CIPN具有多成分、多靶点及多通路的调控特点，其作用机制可能与调控炎症浸润、氧化应激及细胞生长增殖凋亡等多方面相关。
- Abstract:
- Objective To explore the mechanism of Longteng Tongluo Prescription for the treatment of chemotherapy-induced peripheral neuropathy (CIPN) by means of network pharmacology. Methods The active components and action targets of drugs were obtained by TCMSP and UniProt database. With the help of GeneCards, OMIM, TTD, DisGeNET and DrugBank databases, disease-related targets were searched with “chemotherapy-induced peripheral neuropathy” as keywords, and the predictive targets of Longteng Tongluo Prescription acting on CIPN were obtained by intersection of drug action targets and disease targets. The network diagrams of Longteng Tongluo Prescription active component-potential target and common targets of Longteng Tongluo Prescription and CIPN were constructed by Cytoscape 3.7.1 software. The protein-protein interaction network was constructed using STRING database and Cytoscape 3.7.1 software, and the network topology analysis was performed. Metescape database and online mapping tool platform were used for GO and KEGG enrichment analysis. Results Totally 71 active components of Longteng Tongluo Prescription were screened, with 183 target genes and 582 disease-related target genes; 91 drug-disease common target genes were obtained, and the key targets included AKT1, TP53, ALB, VEGFA, JUN, IL-6, CASP3, TNF, STAT3, PTEN, MYC, IL-1β, EGF, HIF1A, ESR1, EGFR and so on. GO functional analysis yielded 1 520 biological processes, 69 cellular components, and 133 molecular functions. The KEGG pathway analysis identified 190 associated signaling pathways related to CIPN, such as pathways in cancer, in cancer proteoglycans, small cell lung cancer, VEGF signaling pathway, NF-КB signaling pathway, and thyroid cancer. Conclusion Longteng Tongluo Prescription in the treatment of CIPN involves the regulation features of multi-components, multi-targets and multi-pathways, and its mechanism may be related to the regulation of inflammatory infiltration, oxidative stress, cell growth, proliferation and apoptosis.
参考文献/References:
[1] Grisold W, Cavaletti G, Windebank A J. Peripheral neuropathies from chemotherapeutics and targeted agents: diagnosis, treatment, and prevention[J]. Neuro Oncology, 2012,14(S4):iv45-iv54.
[2] 曹雯,魏国利,李灵常,等.化疗相关周围神经毒性的治疗进展及中医药防治策略[J].世界科学技术－中医药现代化,2019,21(7):1458-1466.
[3] Waseem M, Kaushik P, Tabassum H, et al. Role of mitochondrial mechanism in chemotherapy-induced peripheral neuropathy[J]. Current Drug Metabolism, 2017,19(1):47-54.
[4] 吕萍.中西医结合治疗奥沙利铂周围神经病变的临床观察[J].中国医药导报,2015,12(21):131-134.
[5] LI S, ZHANG B. Traditional Chinese medicine network pharmacology: theory, methodology and application[J]. Chinese Journal of Natural Medicines, 2013,11(2):110-120.
[6] RU J L, LI P, WANG J N, et al. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines[J]. J Cheminformatics, 2014,6(1):1-6.
[7] UniProt Consortium. UniProt: the universal protein knowledgebase in 2021[J]. Nucleic Acids Res, 2021,49(D1):D480-D489.
[8] Stelzer G, Rosen R, Plaschkes I, et al. The GeneCards suite: from gene data mining to disease genome sequence analyses[J]. Current Protocols in Bioinformatics, 2016, 54(1):1-33.
[9] WANG Y X, ZHANG S, LI F C, et al. Therapeutic target database 2020: enriched resource for facilitating research and early development of targeted therapeutics[J]. Nucleic Acids Research, 2020,48(D1):D1031-D1041.
[10] Pi?ro J, Ramírez-Anguita J M, Saüch-Pitarch J, et al. The DisGeNET knowledge platform for disease genomics: 2019 update[J]. Nucleic Acids Research, 2020,48(D1):D845-D855.
[11] Wishart D S, Feunang Y D, Guo A C, et al. DrugBank 5.0: a major update to the DrugBank database for 2018[J]. Nucleic Acids Research, 2018,46(D1):D1074-D1082.
[12] Szklarczyk D, Gable A L, Lyon D, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets[J]. Nucleic Acids Research, 2019, 47(D1):D607-D613.
[13] ZHOU Y, ZHOU B, Pache L, et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets[J]. Nature Communications, 2019,10(1):1523.
[14] 董超,罗春香,杨润祥.抗肿瘤药物所致神经毒性防治的研究进展[J].重庆医学,2018,47(2):268-272.
[15] 潘传芳,姚琼,祝利民,等.自拟芪藤通络方内服加红艾汤外用对奥沙利铂导致周围神经毒性的影响[J].辽宁中医杂志,2021,48(6):140-142.
[16] 李海,左丽莉,范丽霞,等.化疗药物所致外周神经毒性的防治研究进展[J].河北北方学院学报(自然科学版),2018,34(10):48-51.
[17] Grolleau F, Gamelin L, Boisdroncelle M, et al. A possible explanation for a neurotoxic effect of the anticancer agent oxaliplatin on neuronal voltage-gated sodium channels[J]. Journal of Neurophysiology, 2001,85(5):2293-2297.
[18] Adelsberger H, Quasthoff S, Grosskreutz J, et al. The chemotherapeutic oxaliplatin alters voltage-gated Na+ channel kinetics on rat sensory neurons[J]. European Journal of Pharmacology, 2000,406(1):25-32.
[19] Beijers A J M, Mols F, Vreugdenhil G. A systematic review on chronic oxaliplatin-induced peripheral neuropathy and the relation with oxaliplatin administration[J]. Supportive Care in Cancer, 2014,22(7):1999-2007.
[20] Nodera H, Spieker A, Sung M, et al. Neuroprotective effects of Kv7 channel agonist, retigabine, for cisplatin-induced peripheral neuropathy[J]. Neuroscience Letters, 2011,505(3):223-227.
[21] Argyriou A A, Koltzenburg M, Polychronopoulos P, et al. Peripheral nerve damage associated with administration of taxanes in patients with cancer[J]. Critical Reviews in Oncology and Hematology, 2008,66(3):218-228.
[22] Nabholtz J M, Gelmon K, Bontenbal M, et al. Multicenter, randomized comparative study of two doses of paclitaxel in patients with metastatic breast cancer[J]. Journal of Clinical Oncology, 1996,14(6):1858-1867.
[23] Yan L, Tatsui C E, Rhines L D, et al. Dorsal root ganglion neurons become hyperexcitable and increase expression of voltage-gated T-type calcium channels (Cav3.2) in paclitaxel-induced peripheral neuropathy[J]. Pain, 2016,158(3):417-429.
[24] 孟激光,王凡,韩志海.多发性骨髓瘤伴发周围神经病变机制的研究进展[J].医学综述,2016,22(24):4843-4847.
[25] 饶志璟,邓海滨,祝利民,等.化疗药物所致周围神经毒性中西医研究进展[J].世界科学技术－中医药现代化,2020,22(4):1307-1314.
[26] 徐芃芃,薛鹏,李林潞,等.中西医治疗化疗性周围性神经病变临床研究进展[J].山东中医药大学学报,2018,42(6):565-568.
[27] 张金芝,郑卫红.化疗药致神经毒性的机制及临床治疗的研究进展[J].中国中西医结合杂志,2012,32(2):286-288.
[28] 邹晓玲,陈盼,谢美,等.化疗所致外周神经毒性的中西医治疗进展[J].湖南中医杂志,2018,34(3):200-202.
[29] 罗安明,戎志斌,郭文鹏.“大毒治病,十去其六”理论对放化疗的指导作用[J].中国中医基础医学杂志,2015,21(7):901-902,906.
[30] 王泳,杨建伟,黄争荣,等.黄芪桂枝五物汤防治奥沙利铂所致急性神经毒性的临床观察[J].广西中医药,2018,41(5):20-24.
[31] 孟晶,朱静.中药防治化疗所致周围神经病变的研究进展[J].南京中医药大学学报,2018,34(6):634-638.
[32] 陈藏器.本草拾遗[M].尚志钧,辑校.芜湖:皖南医学院科研科,1983:140.
[33] 王继坤,宋长红,关秀锋.伸筋草的化学成分及药理作用研究进展[J].化学工程师,2021,35(7):55-57.
[34] 国家药典委员会.中华人民共和国药典:一部[M].北京:中国医药科技社,2020:184.
[35] 彭念.吴洋教授运用乌梢蛇伸筋草治疗痹病的临床经验[C]//中国中西医结合学会.2017年第五次世界中西医结合大会论文摘要集(下册).广州,2017:729.
[36] 赵学敏.本草纲目拾遗[M].北京:人民卫生出版社,1963:229.
[37] 范会云,邓乔华,宋松泉.“血分圣药”鸡血藤[J].生命世界,2020(9):52-53.
[38] 邓博,贾立群,程志强,等.鸡血藤干预奥沙利铂致周围神经毒性的Meta分析[J].中华中医药学刊,2016,34(1):20-26.
[39] HUANG J Q, WANG S W, LUO X X, et a1. Cinnamaldehyde reduction of platelet aggregation and thrombosis in rodents[J]. Thrombosis Research, 2007,119(3):337-342.
[40] 张宏宇,陈沫,熊文激.红花黄色素抗血栓和降血脂作用的实验研究[J].中国实验诊断学,2010,14(7):1028-1031.
[41] 黄为飞.中药川乌与草乌的鉴别比较及药理活性分析[J].北方药学,2020,17(12):10-11.
[42] 杨祎辰,常晖,王二欢,等.老鹳草属药用植物化学成分及药理作用研究进展[J].中国现代中药,2021,23(5):918-927.
[43] 郑佳逸,辛贵忠,刘丽芳.威灵仙中的三萜皂苷类成分及其抗关节炎作用机制的研究进展[J].中国野生植物资源,2018,37(5):39-48.
[44] 郑亚平,陈恒晋,沈岚,等.威灵仙的毒副作用研究[J].上海中医药大学学报,2021,35(4):1-11.
[45] 钱深思,刘美怡,容蓉,等.细辛挥发油的化学成分及其药理和毒理现代研究进展[J].中国药物警戒,2021,18(4):388-395.
[46] 马登磊,张兰,李林.淫羊藿提取物的抗炎作用及其机制(英文)[J].生物化学与生物物理进展,2020,47(8):685-699.
[47] 耿胜男,杨莉,李阳杰,等.基于网络药理学的干姜抗癌作用机制分析[J].药物评价研究,2019,42(9):1730-1740,1748.
[48] 冯宁,尚红港.肿瘤坏死因子-α、白介素-6和白介素-8检测在胃癌中的临床价值[J].肿瘤基础与临床,2021,34(3):244-247.
[49] YANG S, WANG Y, MEI K, et al. Tumor necrosis factor receptor 2 (TNFR2)?interleukin-17 receptor D (IL-17RD) heteromerization reveals a novel mechanism for NF-κB activation[J]. Journal of Biological Chemistry, 2015,290(2):861-871.
[50] Pinckard J K, Sheehan K C F, Schreiber R D. Ligand-induced formation of p55 and p75 tumor necrosis factor receptor heterocomplexes on intact cells[J]. Journal of Biological Chemistry, 1997,272(16):10784-10789.
[51] 仇海乐,戎冬文,贾军梅.肿瘤坏死因子-α瘤内注射联合化疗治疗晚期非小细胞肺癌疗效观察[J].肿瘤基础与临床,2020,33(5):404-406.
[52] Arend W P. The balance between IL-1 and IL-1Ra in disease[J]. Cytokine & Growth Factor Reviews, 2002,13(4/5): 323-340.
[53] Pollock G, Pennypacker K R, Mémet S, et al. Activation of NF-κB in the mouse spinal cord following sciatic nerve transection[J]. Experimental Brain Research, 2005,165(4): 470-477.
[54] Smith D, Tweed C, Fernyhough P, et al. Nuclear factor-κB activation in axons and schwann cells in experimental sciatic nerve injury and its role in modulating axon regeneration: studies with etanercept[J]. Journal of Neuropathology and Experimental Neurology, 2009,68(6):691-700.
[55] Lee J A, Hong M, Lee M S, et al. Blood-letting therapy for the common cold: a protocol for a systematic review of controlled trials[J]. Medicine, 2017,96(51):e9315.
[56] 袁华兵,布林,涂源源.NF-κB与周围神经损伤[J].临床合理用药杂志,2010,3(5):124-126.
[57] Peichev M, Naiyer A J, Pereira D, et al. Expression of VEGFR-2 and AC133 by circulating human CD34+ cells identifies a population of functional endothelial precursors[J]. Blood, 2000,95(3):952-958.
[58] 袁一鸣.夹脊电针结合神经松动术对坐骨神经损伤后VEGF、CD34表达及血神经屏障的影响[D].哈尔滨:黑龙江中医药大学,2020.
[59] 陶美惠.电针对大鼠周围面神经再生的作用及其与VEGF/MAPK/ERK信号通路的关系[D].泸州:西南医科大学,2019.
备注/Memo
收稿日期：2021-09-24
更新日期/Last Update:
2022-03-15