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

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。

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

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.