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中国防痨杂志 ›› 2020, Vol. 42 ›› Issue (10): 1115-1120.doi: 10.3969/j.issn.1000-6621.2020.10.018

• 论著 • 上一篇    下一篇

中药治疗肺结核的用药规律及作用机制预测

李婷婷, 刘欢庆, 杜巧盈()   

  1. 710100 西安市胸科医院药物临床试验机构办公室(李婷婷),护理部(杜巧盈);陕西广电网络传媒(集团)股份有限公司集团客户运营公司技术部(刘欢庆)
  • 收稿日期:2020-02-06 出版日期:2020-10-10 发布日期:2020-10-15
  • 通信作者: 杜巧盈 E-mail:931719036@qq.com

Prediction of usage and mechanism of Traditional Chinese Medicine in treating pulmonary tuberculosis

LI Ting-ting*, LIU Huan-qing, DU Qiao-ying()   

  1. *Office of Clinical Trials for Drugs, Xi’an Chest Hospital, Xi’an 710100, China
  • Received:2020-02-06 Online:2020-10-10 Published:2020-10-15
  • Contact: DU Qiao-ying E-mail:931719036@qq.com

摘要:

目的 探索中药治疗肺结核的用药规律,并探讨高频药物的作用机制。方法 通过中国知网数据库和万方医学网检索中文文献,检索词为“肺结核”“中药”;通过PubMed数据库检索外文文献,检索词为“tuberculosis”“traditional Chinese medicine”;检索时间限定为1998年1月1日至2018年12月31日。共检索到相关文献512篇(中文文献405篇,英文文献107篇),最终纳入363篇(中文文献352篇,英文11文献篇)。运用Rapidminer软件进行信息提取,探索中医治疗肺结核的核心中药、常用配伍组合,分析用药规律及药物联用情况。采用BATMAN-TCM数据库获取高频药物的潜在活性成分及作用靶点,采用DisGeNET数据库、治疗靶点数据库(Therapeutic Target Database,TTD)及GeneCards数据库预测和筛选核心中药治疗肺结核的作用靶点,并对药物靶点和疾病靶点进行匹配。采用DAVID数据库对潜在靶点进行GO(Gene Ontology)生物功能及京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)分析。结果 中药治疗肺结核常用补虚药(663次),其次为活血化瘀药(403次)及清热药(325次),出现频次最多的药物为甘草(122次),其次为当归(102次)、生地(99次)、白芍(74次)。配伍组合频次最高的两两药对是甘草-当归(70次),其次为甘草-生地(52次);3味药组合出现频次最高的是甘草-当归-生地(37次),4味药组合出现频次最高的是甘草-当归-生地-白芍(24次)。在生地、白芍配伍时当归也出现的概率为95.0%。筛选出甘草、当归、生地和白芍等4味高频次中药抗结核关键靶点基因92个,可能是通过癌症通路(14个基因)、白细胞跨内皮迁移(13个基因)、自然杀伤细胞介导的细胞毒性(10个基因)、ErbB信号通路(10个基因)等来发挥抗结核作用。结论 肺结核的治疗多以补虚药、活血化瘀药、清热药为主,临床治疗可与甘草、当归、生地、白芍等药配伍使用;高频次药物甘草、当归、生地、白芍治疗肺结核的作用机制可能是通过癌症通路、白细胞跨内皮迁移、自然杀伤细胞介导的细胞毒性、ErbB信号通路来实现。

关键词: 结核, 肺, 中草药, 药物疗法, 联合, 综述文献(主题), 药理作用

Abstract:

Objective To explore the usage of Traditional Chinese Medicine (TCM) in treating pulmonary tuberculosis and the mechanism of frequently used TCM. Methods The relevant Chinese literatures were collected from CNKI database and Wanfang Med Online with the keywords of “pulmonary tuberculosis” and “traditional Chinese medicine”; the foreign literature was collected from PubMed database with the keywords of “tuberculosis” and “traditional Chinese medicine”; the published time was limited from January 1, 1998 to December 31, 2018. A total of 512 related articles were retrieved (405 Chinese literatures, 107 foreign literatures), and 363 articles were included (352 Chinese literatures, 11 foreign literatures) finally. Rapidminer software was used to extracted the information, to explore the key TCM and the common combination for treating tuberculosis, the usage and combination of drugs were analyzed. BATMAN-TCM database was used to obtain the potential active ingredients and targets of frequently used TCM, and the DisGeNET database, Therapeutic Target Database (TTD) and Gene Cards database were used to predict and screen the targets of key TCM for the treatment of tuberculosis, and the drug targets and disease targets were matched. DAVID database was used to analyze the GO (Gene Ontology) biological function and Kyoto Encyclopedia of Genes and Genomes (KEGG). Results Tonic (663 times), activating blood circulation (403 times) and heat-clearing medicines (325 times) were mainly used to treat pulmonary tuberculosis. The most frequently used medicines were liquorice (122 times), chiretta (102 times), rehmanniae praeparatum (99 times) and paeoniae alba (74 times). The most frequently used two-drug pair compatibility were liquorice-chiretta (70 times) and liquorice-rehmanniae praeparatum (52 times). The liquorice-chiretta-rehmanniae praeparatum was the most frequently used three-drug pair (37 times), and liquorice-chiretta-rehmanniae praeparatum-paeoniae alba was used most as four-drug pair (24 times). When rehmanniae praeparatum compatible with paeoniae alba, the usage rate of chiretta was 95.0%. A total of screened 92 key targets against tuberculosis of 4 frequently used TCM (liquorice, chiretta, rehmanniae praeparatum, paeoniae alba) were found, which may play the role of anti-tuberculosis through cancer pathways (14 targets), leukocyte trans-endothelial migration (13 targets), natural killer cell mediated cytotoxicity (10 targets), and ErbB signaling pathway (10 targets). Conclusion The treatment of tuberculosis mainly use consists of tonic, activating blood circulation and heat-clearing medicines. Liquorice, chiretta, rehmanniae praeparatum and paeoniae alba could be used in clinical treatment. The mechanism of these 4 frequently used TCM in treating tuberculosis may be act through cancer pathway, leukocyte trans-endothelial migration pathway, natural killer cell mediated cytotoxicity pathway and ErbB signaling pathway.

Key words: Tuberculosis, pulmonary, Drugs, Chinese herbal, Drug therapy, combination, Review literature as topic, Pharmacologic actions