[关键词]
[摘要]
目的 基于 Meta 分析、网络药理学和分子对接对冬虫夏草治疗慢性肾病的安全性、有效性及机制进行 系统评价和分析验证。方法 检索中国知网(CNKI)和 PubMed 等 6 个常用中英文数据库,筛选出冬虫夏草制 剂(百令胶囊、金水宝胶囊)治疗慢性肾病随机对照试验的相关文献,使用 RevMan5.3 和 Stata17.0 对纳入的文 献进行 Meta 分析。从 HERB 数据库搜集到冬虫夏草的活性成分,在 GeneCards、OMIM 和 Disgenet 数据库中筛 选慢性肾病的靶点,采用 Cytoscape 3.9.1 构建“药物-成分-靶点(含 PPI)-通路”网络进行核心成分和靶点筛 选。结果 Meta 分析共纳入 30 项临床研究,共 2 882 例患者,试验组 1 441 例,对照组 1 441 例,确定结局 指标为血肌酐(Scr)、尿素氮(BUN)、肌酐清除率(CCR)、24 h 尿蛋白定量(24 h UPQ)、白细胞介素 6(IL-6)、 肿瘤坏死因子 α(TNF-α),冬虫夏草制剂联合常规治疗慢性肾病,其临床总有效率(RR=1.19,95%CI[1.15~ 1.23],P<0.000 01)、血肌酐(SMD=-1.13,95%CI[-1.37~-0.88],P<0.000 01)、尿素氮(SMD=-1.06,95%CI [-1.28~-0.84],P<0.000 01)、肌酐清除率(SMD=0.98,95%CI[0.74~1.22],P<0.000 01)、24 h 尿蛋白定量 (SMD=-1.03,95%CI[-1.24~ -0.81],P<0.000 01)、IL-6(SMD=-1.73,95%CI[-2.21~ -1.24],P<0.000 01)、 TNF-α(SMD=-1.77,95%CI[-2.36~-1.17],P<0.000 01)。随机对照试验明确不良反应者 18 例,主要症状为胃 肠道不适或皮肤瘙痒。通过生物信息学分析,筛选出冬虫夏草的 52 种有效成分,靶点 2 534 个,关键活性成 分为脱酮素、尿嘧啶和脱氧穿心莲内酯等, 可能通过作用于 SRC、HSP90AA1、AKT1 等关键靶点,调节 AGE-RAGE、PI3K-Akt、MAPK、HIF-1 等信号通路,减轻炎症和氧化应激,抑制纤维化,从而达到治疗慢性 肾病的作用。结论 该研究表明,冬虫夏草通过调控多个关键信号通路,能够显著提高抗慢性肾病的临床总有 效率,在改善肾功能和减轻炎症方面表现出多重优势,同时具有良好的安全性,应用前景广阔,值得进一步深 入研究与推广。
[Key word]
[Abstract]
Objective To systematically evaluate and validate the safety,efficacy,and mechanism of Cordyceps in treating chronic kidney disease (CKD) based on Meta-analysis, network pharmacology, and molecular docking. Methods Six commonly used Chinese and English databases,including CNKI and PubMed,were searched to identify randomized controlled trials (RCTs) on Cordyceps preparations (Bailing Capsules,Jinshuibao Capsules) for CKD treatment. RevMan 5.3 and Stata 17.0 were used for Meta-analysis of the included studies. Active components of Cordyceps were collected from the HERB database,and CKD-related targets were screened from GeneCards,OMIM, and Disgenet databases. Cytoscape 3.9.1 was used to construct a “drugs-components-targets (including PPI) -pathways” network for screening core components and targets. Results The Meta-analysis included 30 clinical studies with 2 882 patients (1 441 in the experimental group and 1 441 in the control group) . Outcome measures included serum creatinine (Scr),blood urea nitrogen (BUN),creatinine clearance rate (CCR),24-hour urinary protein (24 h UP),interleukin-6 (IL-6),and tumor necrosis factor-α (TNF-α). Cordyceps preparations combined with conventional treatment significantly improved the overall clinical efficacy (RR = 1.19, 95%CI [1.15-1.23], P< 0.000 01),Scr (SMD = -1.13,95%CI [-1.37 to -0.88],P<0.000 01),BUN (SMD = -1.06,95% CI [-1.28 to -0.84],P<0.000 01),and 24 h UP (SMD = -1.03,95%CI [-1.24 to -0.81],P<0.000 01),CCR (SMD = 0.98, 95%CI [0.74-1.22],P<0.000 01),and IL-6 (SMD = -1.73,95%CI [-2.21 to-1.24],P<0.000 01) and TNF-α (SMD = -1.77, 95%CI [-2.36 to -1.17], P<0.000 01). Adverse reactions were reported in 18 cases, primarily gastrointestinal discomfort or skin itching. Bioinformatics analysis identified 52 active components and 2 534 targets of Cordyceps,with key active components including cordycepin,uracil,and deoxyandrographolide. These components may act on key targets such as SRC,HSP90AA1,and AKT1,regulating signaling pathways such as AGE-RAGE, PI3K-Akt, MAPK, and HIF-1, thereby alleviating inflammation and oxidative stress, inhibiting fibrosis, and achieving therapeutic effects on CKD. Conclusion This study demonstrates that Cordyceps significantly improves the overall clinical efficacy of CKD treatment by regulating multiple key signaling pathways,showing multiple advantages in improving renal function and reducing inflammation, with good safety and broad application prospects, warranting further in-depth research and promotion.
[中图分类号]
R285.6
[基金项目]
青海省重大科技专项(2021-SF-A4-3);2021年青海省“昆仑英才高端创新创业人才”拔尖人才项目;三江源国家公园联合研究专项 (LHZX-2022-01)