玉屏风散治疗慢性肾小球肾炎的临床疗效评价及作用机制研究

Yu Ping Feng Powder for chronic glomerulonephritis treatment:A meta-analysis and network pharmacology study

本研究通过meta分析评价玉屏风散(YPF)治疗慢性肾小球肾炎(CGN)的临床疗效,并利用网络药理学和分子对接探讨其作用机制。检索国内外数据库CNKI、维普、中国生物医学、万方、PubMed和Cochrane建库至2023年5月YPF治疗CGN临床随机对照试验,根据纳入和排除标准,纳入研究。运用RevMan5.4软件进行质量评估和meta分析,使用TSABeta软件对主要结局指标进行序贯分析。通过TCMSP、GeneC ards、OMIM、TTD数据库检索YPF的有效成分及CGN靶点,利用Venny2.1.0获取两者交集靶点,运用DAVID数据库进行GO和KEGG富集分析。通过AutoDockVina1.5.6软件进行分子对接。共纳入14项研究,1072名患者。meta分析结果显示,YPF在治疗CGN的临床总有效率[OR=6.99,95%CI(4.68,10.44)],证候改善率[OR=3.16,95%CI(1.43,6.98)],降低24小时尿蛋白[SMD=–1.90,95%CI(–2.54,–1.25)]、血清肌酐[SMD=–0.38,95%CI(–0.57,–0.19)],尿素氮[SMD=–0.46,95%CI(–0.63,–0.30)],均具有统计学意义(P<0.05)。序贯分析结果表明,本次meta结果是可靠的,YPF治疗CGN的总有效率优于单纯西药治疗。网络药理学共筛选出槲皮素、山奈酚、汉黄芩素等45种有效成分,关键靶点有TNF、AKT1、IL-6和VEGF等,涉及AGE-RAGE、TNF、PI3K-AKT等信号通路。分子对接显示,槲皮素、山奈酚、汉黄芩素等与关键靶点可稳定结合,结合能均≤–6.0 kJ/mol。结果发现,YPF对CGN是一种积极的治疗措施,其作用机制可能与多种成分、多个靶点、多条信号通路产生的免疫调节、抗炎、抗氧化和抗纤维化有关。

Chronic glomerulonephritis(CGN)is a common kidney disease and the leading cause of renal failure.This not only affects the quality of life of patients but also places a significant burden on their families.The objective of this study was to evaluate the clinical efficacy of Yu Ping Feng Powder(YPF)in treating CGN through meta-analysis and trial sequential analysis(TSA).Additionally,network pharmacology and molecular docking were employed to explore the mechanisms of YPF.We conducted a comprehensive search of the China National Knowledge Infrastructure(CNKI),VIP Database,Sinomed,WanFang,PubMed,and Cochrane Library up until May 2023.Quality assessment and meta-analysis were performed using the RevMan 5.4 software.TSA of key outcome indicators was conducted using TSA Beta software.The active ingredients of YPF were obtained from the TCMSP database,while the CGN targets were sourced from the GeneCards,OMIM,and TTD databases.The shared targets between YPF and CGN were identified using the STRING database and analyzed using Cytoscape 3.7.2 software.GO and KEGG analyses were employed to predict potential pathways affected by YPF in CGN.Finally,molecular docking techniques were utilized to investigate the interactions between core components and targets.The results of the meta-analysis revealed that YPF-based treatment for CGN significantly improved total clinical effectiveness,evidence-based outcomes,and reductions in 24-h urine protein,serum creatinine,and urea nitrogen compared to conventional treatment.Network pharmacology analysis identified TNF,AKT1,IL-6,and VEGFA as key targets for CGN treatment.Molecular docking predicted that the most active ingredients in YPF for CGN were quercetin,kaempferol,and wogonin.YPF demonstrated positive effects in treating CGN through multiple signaling pathways,leading to immunomodulatory,anti-inflammatory,antioxidant,and anti-fibrotic effects.