山东大学耳鼻喉眼学报 ›› 2022, Vol. 36 ›› Issue (3): 226-236.doi: 10.6040/j.issn.1673-3770.0.2021.505

• 临床研究 • 上一篇    下一篇

基于Meta分析桥接网络药理学的鼻渊通窍颗粒治疗慢性鼻窦炎的疗效评价及潜在机制研究

姜雪莲1, 张静月1, 卫旭东1,2,3   

  1. 1. 兰州大学第一临床医学院, 甘肃 兰州 730099;
    2. 甘肃省人民医院 耳鼻咽喉头颈外科, 甘肃 兰州 730013;
    3. 甘肃中医药大学第一临床医学院, 甘肃 兰州 730099
  • 发布日期:2022-06-15
  • 通讯作者: 卫旭东. E-mail:weixd93@lzu.edu.cn
  • 基金资助:
    国家自然科学基金项目(81860475);甘肃省人民医院国家科研项目培养计划重点项目(19SYPYA-13);甘肃中医药大学科学研究与创新基金项目(2020KCZD-7);甘肃省自然科学基金项目(17JR5RA214)

Evaluation of the efficacy and potential mechanism of biyuan tongqiao granules in chronic sinusitis treatment based on Meta-analysis bridging network pharmacology

JIANG Xuelian1, ZHANG Jingyue1, WEI Xudong1,2   

  1. 1. The First School of Clinical Medicine, Lanzhou University, Lanzhou 730099, Gansu, China;
    2. Department of Otorhinolaryngology & Head and Neck Surgery, Gansu Provincial Hospital, Lanzhou 730013, Gansu, China;
    3. The First School of Clinical Medicine, Gansu University of Chinese Medicine, Lanzhou 730099, Gansu, China
  • Published:2022-06-15

摘要: 目的 基于Meta分析对鼻渊通窍颗粒及克拉霉素治疗慢性鼻窦炎的疗效进行评价及通过网络药理学对鼻渊通窍颗粒治疗慢性鼻窦炎的潜在机制进行研究。 方法 计算机检索Web of Science、PubMed、EMBASE、中国期刊全文数据库(CNKI)、维普全文数据库(VIP)和万方数据库文献(建库~2021年11月),检索鼻渊通窍颗粒在慢性鼻窦炎治疗方面的文献并进行筛选,选取随机对照实验(RCT),对符合纳入标准的文献进行质量评价,并使用RevMan5.3软件对符合质量标准的研究进行Meta分析。鼻渊通窍颗粒靶点通过TCMSP与BATMAN-TCM数据库进行筛选,利用Genecards数据库、OMIM数据库、Drug bank数据库、Pharmgkb数据库筛选慢性鼻窦炎靶点,通过FunRich软件获得共有靶点,使用DAVID平台对鼻渊通窍颗粒-慢性鼻窦炎共有靶点进行基因本体生物进程及京都基因与基因组百科全书通路分析,基于Cytoscape软件进行关键靶点筛选。 结果 纳入8篇原始研究,共包括1 018例患者,其中治疗组530例,对照组488例,结果治疗组为单用鼻渊通窍颗粒临床有效率[RR=1.15,95%CI(1.05,1.27),Z=2.91,P=0.004],治疗组为鼻渊通窍颗粒联合克林霉素临床有效率[RR=1.31,95%CI(1.18,1.45),Z=5.14,P<0.000 01],差异均具有统计学意义;治疗组为鼻渊通窍颗粒联合克林霉素,对照组为克林霉素组,VAS评分[MD=-7.15,95%CI(-8.22,-6.08),Z=13,P<0.000 01],差异具有统计学意义;Lund-Kennedy评分[MD=-2.68,95%CI(-4.64,-0.72),Z=2.68,P=0.007],差异具有统计学意义。网络药理学获得共有靶点48个,KEGG富集的通路主要包括HIF-1信号传导通路、Toll样受体信号传导途径、NOD样受体信号传导途径、NF-κB信号传导途径,其中鼻渊通窍颗粒治疗慢性鼻窦炎发挥作用的关键靶点为TNF、IL6、AKT1、VEGFA、PTGS2。 结论 无论是鼻渊通窍颗粒联合使用克拉霉素还是单用鼻渊通窍颗粒相关结局说明其治疗效果均优于单用克拉霉素,受纳入研究质量的限制,上述结论尚需展开更多高质量的研究予以验证,而鼻渊通窍颗粒治疗慢性鼻窦炎发挥作用的关键靶点为TNF、IL6、AKT1、VEGFA、PTGS2。

关键词: 鼻渊通窍颗粒, 慢性鼻窦炎, Meta分析, 网络药理学, 疗效评价

Abstract: Objective The efficacy of biyuan tongqiao granules and clarithromycin in the treatment of chronic rhinosinusitis was evaluated in this study. Based on Meta-analysis and network pharmacology, the potential mechanism of biyuan tongqiao granules and clarithromycin in chronic rhinosinusitis treatment was investigated. Methods Web of Science, PubMed, EMBASE, China journal full text database(CNKI), Vipers full text database(VIP), and Wanfang database literature(established since November 2021)were used to retrieve and screen the literature on chronic rhinosinusitis treatment using biyuan tongqiao granules. Randomized controlled trials(RCTs)were selected, and the quality of the literature that met the inclusion criteria was evaluated. Meta-analysis was performed for studies that met the quality criteria using RevMan 5.3 software. Target nasal abnormalities were screened using the TCMSP and BATMAN-TCM databases. Chronic sinusitis targets were screened using the GeneCards database, OMIM database, drug bank database, and PharmGKB database. Both targets, nasal abnormalities and chronic sinusitis, were screened using the FunRich software. The DAVID platform was used to conduct gene ontology biological processes, Kyoto gene, and genome encyclopedia pathway analysis on the shared targets of chronic rhinosinusitis. Key target screening was performed using the Cytoscape software. Results Eight original studies with a total of 1018 patients were included, among these 530 patients were in the treatment group and 488 patients in the control group. The clinical efficiency of biyuan tongqiao granules alone in the treatment group [RR=1.15, 95%CI(1.05, 1.27], Z=2.91, P=0.004)and the clinical efficiency of biyuan tongqiao granules combined with clindamycin in the treatment group [RR=1.31. 95%CI(1.18, 1.45), Z=5.14, P<0.000 01] were significantly different. The VAS scores(MD=-7.15, 95%CI(-8.22, -6.08), Z=13, P<0.000 01)in the treatment group for biyuan tongqiao granules combined with clindamycin and in the control group for clindamycin were also significantly different. The Lund-Kennedy score [MD=-2.68, 95%CI(-4.64, -0.72), Z=2.68, P=0.007] was significantly different. Network pharmacology identified a total of 48 targets and the KEGG-enriched pathways included the HIF-1 signaling pathway, Toll-like receptor signaling pathway, NOD-like receptor signaling pathway, and NF-kappa B signaling pathway. The key targets in the treatment of chronic sinusitis were TNF, IL6, AKT1, VEGFA, and PTGS2. Conclusion The combination of biyuan tongqiao granules with clarithromycin or biyuan tongqiao granules alone indicated that their therapeutic effects were better than those of clarithromycin alone. Due to the limitation of the quality of included studies, more high-quality studies are required to validate the above findings. Key targets for the effects of biyuan tongqiao granules in the treatment of chronic rhinosinusitis are TNF, IL6, AKT1, VEGFA, and PTGS2.

Key words: Biyuan tongqiao granules, Chronic rhinosinusitis, Meta-analysis, Network pharmacology, Evaluation of the efficacy

中图分类号: 

  • R765.4+1
[1] 中华耳鼻咽喉头颈外科杂志编辑委员会鼻科组.慢性鼻-鼻窦炎诊断和治疗指南(2012年,昆明)[J]. 中华耳鼻咽喉头颈外科杂志, 2013(2): 92-94. doi: 10.3760/cma.j.issn.1673-0860.2013.02.002.
[2] Biswas K, Chang A, Hoggard M, et al. Toll-like receptor activation by sino-nasal mucus in chronic rhinosinusitis[J]. Rhinology, 2017, 55(1): 59-69. doi: 10.4193/Rhin16.201.
[3] Demirdag YY, Ramadan HH. Direct measurement of upper airway inflammation in children with chronic rhinosinusitis: implications for asthma[J]. Curr Opin Allergy Clin Immunol, 2016, 16(1): 18-23. doi: 10.1097/ACI.0000000000000237.
[4] 王悦, 慢性鼻窦炎应用鼻渊通窍颗粒的治疗效果及对鼻纤毛传输功能的影响[J]. 养生保健指南, 2018(48): 247. doi: 10.3969/j.issn.1006-6845.2018.48.239.
[5] 陈宇, 丁科全, 何雯等. 克拉霉素强化治疗慢性鼻窦炎的临床观察[J]. 中国卫生标准管理, 2020, 11(3): 89-91. CHEN Yu, DING Kequan, HE Wen, et al. Clinical observation of intensive treatment of chronic sinusitis with clarithromycin[J]. China Health Standard Management, 2020, 11(3): 89-91.
[6] 王士贞. 中医耳鼻咽喉科学[M]. 2版. 北京:中国中医药出版社, 2007.
[7] 中华医学会耳鼻咽喉科学分会. 慢性鼻窦炎鼻息肉临床分型分期及内窥镜鼻窦手术疗效评定标准(1997年, 海口)[J]. 中华耳鼻咽喉科杂志, 1998(3): 6.
[8] 陈旎珺, 吴继昌, 胡原, 等. 鼻渊通窍颗粒联合克拉霉素治疗小儿慢性鼻窦炎的临床疗效及对炎性反应因子的影响[J]. 世界中医药, 2019, 14(7): 1780-1783, 1788. doi:10.3969/j.issn.1673-7202.2019.07.033. CHEN Nijun, WU Jichang, HU Yuan, et al. Clinical effects of biyuan Tongqiao Granule combined with clarithromycin in children with chronic sinusitis and its influence on inflammatory factors[J]. World Chinese Medicine, 2019, 14(7): 1780-1783, 1788. doi:10.3969/j.issn.1673-7202.2019.07.033.
[9] 洪海裕, 陈奕伸, 洪仲思, 等. 鼻渊通窍颗粒联合克拉霉素治疗不伴息肉的慢性鼻-鼻窦炎疗效观察[J]. 中药材, 2015, 38(6): 1334-1336. doi:10.13863/j.issn1001-4454.2015.06.057.
[10] 林君. 鼻渊通窍颗粒联合克拉霉素颗粒治疗小儿慢性鼻窦炎的疗效观察[J]. 中国现代医生, 2014, 52(32): 34-36. LIN Jun. The effect of Biyuan Tongqiao Granule combined clarithromycin granules on children with chronic sinusitis[J]. China Modern Doctor, 2014, 52(32): 34-36.
[11] 林响, 曹时珍. 鼻渊通窍颗粒辅助治疗小儿慢性鼻窦炎的可行性及安全性[J]. 慢性病学杂志, 2017, 18(11): 1294-1295, 1298. doi:10.16440/j.cnki.1674-8166.2017.11.036.
[12] 向华, 杨飞, 周意, 等. 鼻渊通窍颗粒联合克拉霉素治疗小儿慢性鼻窦炎的临床疗效[J]. 医学综述, 2017, 23(5): 1038-1040. doi:10.3969/j.issn.1006-2084.2017.05.045. XIANG Hua, YANG Fei, ZHOU Yi, et al. Effect of biyuan Tongqiao Granule combined with clarithromycin in treatment of pediatric chronic sinusitis[J]. Medical Recapitulate, 2017, 23(5): 1038-1040, 3. doi:10.3969/j.issn.1006-2084.2017.05.045.
[13] 郑顺昌, 杨娟娟. 鼻渊通窍颗粒治疗儿童慢性鼻窦炎85例疗效观察[J]. 山东医药, 2010, 50(37): 93. doi: 10.3969/j.issn.1002-266X.2010.37.066.
[14] 楚选云, 高建步. 鼻渊通窍颗粒治疗慢性鼻-鼻窦炎的效果及对鼻纤毛传输功能的影响[J]. 世界中医药, 2018, 13(5):1191-1194. 10.3969/j.issn.1673-7202.2018.05.035. CHU Xuanyun, GAO Jianbu. Efficacy of biyuan tongqiao granules in treating chronic sinusitis and effects on nasal ciliary transmission[J]. World Chinese Medicine, 2018, 13(5):1191-1194. 10.3969/j.issn.1673-7202.2018.05.035.
[15] 李华斌, 赖玉婷, 姜文秀. 慢性鼻窦炎的内表型研究进展及精准治疗[J]. 山东大学耳鼻喉眼学报, 2019, 33(3): 9-13. doi: 10.6040/j.issn.1673-3770.1.2018.043. LI Huabin, LAI Yuting, JIANG Wenxiu. Endotypes and precision medicine in chronic sinusitis treatment[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2019, 33(3): 9-13. doi: 10.6040/j.issn.1673-3770.1.2018.043.
[16] 娄鸿飞, 王成硕. 慢性鼻窦炎分型研究进展[J]. 山东大学耳鼻喉眼学报, 2018, 32(3): 10-13. doi: 10.6040/j.issn.1673-3770.1.2018.008. LOU Hongfei, WANG Chengshuo. Progress in classification of chronic sinusitis[J]. Journal of Otolaryngology and Ophthalmology of Shandong University, 2018, 32(3): 10-13. doi: 10.6040/j.issn.1673-3770.1.2018.008.
[17] 黄颖睿, 林亚明. 中医治疗慢性鼻窦炎的临床进展[J]. 云南中医中药杂志, 2021, 42(10): 86-88. doi:10.16254/j.cnki.53-1120/r.2021.10.023.
[18] 许政敏, 李博, 张建基, 等. 鼻渊通窍颗粒治疗儿童鼻部炎症专家共识[J]. 中国实用儿科杂志, 2021, 36(8): 561-564. doi:10.19538/j.ek2021080601. XU Zhengmin, LI Bo, ZHANG Jianji, et al. Expert consensus on the treatment of childhood rhinitis with Biyuan Tongqiao Granules[J]. Chinese Journal of Practical Pediatrics, 2021, 36(8): 561-564. doi:10.19538/j.ek2021080601.
[19] Cho HJ, Kim CH. Oxygen matters: hypoxia as a pathogenic mechanism in rhinosinusitis[J]. BMB Rep, 2018, 51(2): 59-64. doi:10.5483/bmbrep.2018.51.2.014.
[20] Do NY, Shin HJ, Lee JE. Wheatgrass extract inhibits hypoxia-inducible factor-1-mediated epithelial-mesenchymal transition in A549 cells[J]. Nutr Res Pract, 2017, 11(2): 83-89. doi:10.4162/nrp.2017.11.2.83.
[21] 尹文华, 刘素琴, 陈志凌, 等. 缺氧诱导因子1α与黏蛋白5在慢性鼻-鼻窦炎组织中的表达与意义[J]. 中国耳鼻咽喉头颈外科, 2016, 23(11): 632-636. doi:10.16066/j.1672-7002.2016.11.004. YIN Wenhua, LIU Suqin, CHEN Zhiling, et al. Expression of hypoxia-inducible factor-1α mRNA and MUC5 in chronic rhinosinusitis and their correlation[J]. Chinese Archives of Otolaryngology-Head and Neck Surgery, 2016, 23(11): 632-636. doi:10.16066/j.1672-7002.2016.11.004.
[22] 王银鑫, TLR2、TLR4在真菌球型鼻窦炎的表达及意义[D]. 新乡,新乡医学院, 2020.
[23] Rai G, Das S, Ansari MA, et al. TLR-2 expression and dysregulated human Treg/Th17 phenotype in Aspergillus flavus infected patients of chronic rhinosinusitis with nasal polyposis[J]. Microb Cell Fact, 2020, 19: 215. doi:10.1186/s12934-020-01481-3.
[24] 张岳, 唐年亚. 补肺益脾通窍汤对慢性鼻窦炎家兔模型NF-κB p65的影响[J]. 中医研究, 2016, 29(1): 65-67. doi:10.3969/j.issn.1001-6910.2016.01.28.
[25] Yang HW, Kim HJ, Park JH, et al. Apigenin alleviates TGF-β1-induced nasal mucosa remodeling by inhibiting MAPK/NF-kB signaling pathways in chronic rhinosinusitis[J]. PLoS One, 2018, 13(8): e0201595. doi:10.1371/journal.pone.0201595.
[26] Jung HJ, Zhang YL, Kim DK, et al. The role of NF-κB in chronic rhinosinusitis with nasal polyps[J]. Allergy Asthma Immunol Res, 2019, 11(6): 806. doi:10.4168/aair.2019.11.6.806.
[27] 陈雨, 徐志猛, 李萍. 钙离子信号介导Nod样受体蛋白炎性小体激活的研究进展[J]. 中国药科大学学报, 2021, 52(5): 513-521. doi:10.11665/j.issn.1000-5048.20210501. CHEN Yu, XU Zhimeng, LI Ping. Calcium signal-mediated activation of NLRP3 inflammasome[J]. Journal of China Pharmaceutical University, 2021, 52(5): 513-521. doi:10.11665/j.issn.1000-5048.20210501.
[28] Qing X, Zhang YQ, Peng Y, et al. miR-142-3p regulates inflammatory response by contributing to increased TNF-α in chronic rhinosinusitis with nasal polyposis[J]. Ear Nose Throat J, 2021, 100(1): NP50-NP56. doi:10.1177/0145561319847972.
[29] 陈薇, 刘仲娟, 叶菁. 慢性鼻-鼻窦炎鼻黏膜中糖原合成酶激酶3β与PI3K/Akt及白细胞介素6间的相关性[J]. 中华耳鼻咽喉头颈外科杂志, 2013, 48(2): 128-134. doi:10.3760/cma.j.issn.1673-0860.2013.02.017. CHEN Wei, LIU Zhongjuan, YE Jing. Relationship among the expression of GSK3β, PI3DK/Akt, and IL-6 in chronic rhinosinusitis[J]. Chinese Journal of Otorhinolaryngology Head and Neck Surgery, 2013, 48(2): 128-134. doi:10.3760/cma.j.issn.1673-0860.2013.02.017.
[30] Pietruszewska W, Fendler W, Podwysocka M, et al. Expression of transcript variants of PTGS1 and PTGS2 genes among patients with chronic rhinosinusitis with nasal polyps[J]. Diagnostics(Basel), 2021, 11(1): 135. doi:10.3390/diagnostics11010135.
[31] Shi LL, Ma J, Deng YK, et al. Cold-inducible RNA-binding protein contributes to tissue remodeling in chronic rhinosinusitis with nasal polyps[J]. Allergy, 2021, 76(2): 497-509. doi:10.1111/all.14287.
[32] Tian TF, Q Yuan, J Ye, et al. Relationship and significance among IL-6,PI3K/Akt and GSK 3β in chronic rhinosinusitis[J]. Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi, 2016, 30(23): 1859-1864. doi: 10.13201/j.issn.1001-1781.2016.23.006.
[1] 敖天, 程雷. 慢性鼻窦炎伴鼻息肉的内型研究及其指导下的精准控制与治疗[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 7-14.
[2] 熊攀辉,沈暘,杨玉成. 基于表型和内在型的慢性鼻窦炎诊治进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 15-19.
[3] 姚爽,娄鸿飞. 慢性鼻窦炎的内在型研究进展及精准医疗[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 20-29.
[4] 石帅,郑泉,程雷. 度普利尤单抗在慢性鼻窦炎伴鼻息肉治疗中的研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 36-42.
[5] 王欢,胡俐,余洪猛. 慢性鼻窦炎相关嗅觉功能障碍研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 43-49.
[6] 宜若男,陈福权. 嗜酸性粒细胞与嗅觉功能障碍[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 50-55.
[7] 谷钰,万鑫,肖自安. 中性粒细胞和嗜酸性粒细胞在慢性鼻窦炎中的相互影响及临床治疗思考[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 56-63.
[8] 林海,朱莹,张维天. 慢性鼻窦炎发病中离子通道作用研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 64-70.
[9] 乔新杰,赵玉林. 慢性鼻窦炎中上皮间质转化信号转导通路及其他相关因子的研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 71-77.
[10] 黄丹怡,张婷,陈静,张薇. 上皮屏障在慢性鼻窦炎伴鼻息肉中的研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 78-83.
[11] 李佳倪,朱冬冬,孟粹达. 表观遗传学在慢性鼻窦炎伴鼻息肉发病机制中的作用[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 84-91.
[12] 曹轩,肖旭平,李云秋. 透明质酸在慢性鼻窦炎中的研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 104-109.
[13] 刘一潼,周穗子,邱前辉. NLRP3炎症小体在慢性鼻窦炎和变应性鼻炎中的研究进展[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 142-146.
[14] 王露,谢慧,卢美迪,邓新星,李清韵. 基于网络药理学和分子对接探讨“川芎-白芷”药对治疗鼻窦炎的作用机制[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 154-164.
[15] 刘厚军,张倩,程友,薛飞,许莉,吴明海. 慢性鼻窦炎伴双侧鼻息肉的发病与RANTES基因多态性的关系分析[J]. 山东大学耳鼻喉眼学报, 2022, 36(3): 165-170.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
[1] 和守盰,陈 斌,殷善开,苏开明,姜 晓 . OSAHS患者UPPP手术前后上气道形态学变化[J]. 山东大学耳鼻喉眼学报, 2008, 22(5): 385 -388 .
[2] 宋西成,张庆泉,夏永宏,刘鲁沂,于鲁欣,王 郜,姜秀良 . 阻塞性睡眠呼吸暂停低通气综合征患者的术后ICU监护[J]. 山东大学耳鼻喉眼学报, 2008, 22(5): 389 -392 .
[3] 薛卫国,孙洁,金铮,石文斌,辛露,林国经,李加耘 . 盐酸左氧氟沙星滴耳液治疗中耳炎的疗效观察[J]. 山东大学耳鼻喉眼学报, 2006, 20(4): 300 -303 .
[4] 张庆泉,李新民,王 强,王有福 . 鼻内镜下犬齿窝径路治疗上颌窦病变[J]. 山东大学耳鼻喉眼学报, 2007, 21(1): 38 -39 .
[5] 董 频,李晓艳,屠理强,孟晴虹,王 桑,谢 晋,姜 彦 . 晚期下咽癌、喉复发癌术后颈部缺损整复组织的选择[J]. 山东大学耳鼻喉眼学报, 2007, 21(5): 385 -387 .
[6] 姜绍红,朱宇宏,王 强,宋西成 . 难治性原发性鼻出血101例[J]. 山东大学耳鼻喉眼学报, 2007, 21(6): 542 -544 .
[7] 王昭迪,时光刚 . 虚拟现实技术在鼻外科的应用[J]. 山东大学耳鼻喉眼学报, 2008, 22(1): 74 -77 .
[8] 雷迅1 ,刘强和1 ,孔中雨1 ,向秋2 ,耿宛平1 ,黄辉3 ,董译元1 ,刘芳贤1
. EGCG对鼻咽癌细胞株裸鼠移植瘤的放疗增敏作用以及对Survivin表达的影响[J]. 山东大学耳鼻喉眼学报, 2009, 23(1): 6 -9 .
[9] 吴世普
. 鼻内镜下联合下鼻道开窗治疗上颌窦真菌球15例[J]. 山东大学耳鼻喉眼学报, 2009, 23(2): 73 -74 .
[10] 刘伟,殷团芳,任基浩. 中耳胆脂瘤的发生及其与细胞凋亡的关系[J]. 山东大学耳鼻喉眼学报, 2010, 24(01): 29 -33 .