[关键词]
[摘要]
目的 基于动物实验、网络药理学与分子对接技术,探究岭南中药高良姜治疗脓毒症急性肾损伤(SAKI)的效果及潜在作用机制。方法 通过ip脂多糖(LPS)构建脓毒症小鼠模型,经不同剂量高良姜治疗后检测生存曲线、血清炎症因子及肾功能指标,阐明高良姜对SAKI的疗效。通过多个数据库获取高良姜的成分靶点及SAKI的疾病靶点,分析交集靶点并经蛋白质-蛋白质相互作用(PPI)网络分析筛选核心靶点,结合基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析高良姜的作用机制,最后通过分子对接、动力学模拟验证活性成分及靶点之间的相互关系。结果 动物实验显示,脓毒症后小鼠生存率显著降低、炎症因子[肿瘤坏死因子-α(TNF-α)、白细胞介素(IL)-6、IL-1β]及肾损伤指标[肌酐(Scr)、尿素氮(BUN)]显著升高,高良姜治疗后上述指标呈剂量相关性改善。通过网络药理学筛选出322个高良姜的潜在治疗靶点、进一步分析得到12个核心靶点,富集分析显示高良姜对SAKI的作用机制主要聚焦信号传导、凋亡调控、炎症抑制及缺氧应答等方面,分子对接及药动学模拟表明靶点表皮生长因子受体(EGFR)与活性成分麦角异柯宁碱、7,2'-二羟基黄酮结合稳定性良好。结论 高良姜可通过活性成分与关键靶点协同调控多通路,抑制炎症反应、改善肾功能,为SAKI的治疗提供潜在药物和理论依据。
[Key word]
[Abstract]
Objective Based on animal experiments, network pharmacology and molecular docking technology, to explore the effect and potential mechanism of Lingnan traditional Chinese medicine Alpinia officinarum in the treatment of sepsis-associated acute kidney injury (SAKI). Methods A mouse model of sepsis was established by intraperitoneal injection of LPS. After treatment with different doses of A. officinarum, the survival curve, serum inflammatory factors and renal function indexes were detected to clarify the efficacy of A. officinarum on SAKI. The component targets of A. officinarum and the disease targets of SAKI were obtained through multiple databases. The intersection targets were analyzed and the core targets were analyzed and screened by PPI network. The mechanism of action of A. officinarum was analyzed by GO and KEGG enrichment. Finally, the relationship between active components and targets was verified by molecular docking and kinetic simulation. Results Animal experiments showed that the survival rate of mice after sepsis was significantly reduced, and inflammatory factors (TNF-α, IL-6, IL-1β) and renal injury indicators (Scr, BUN) were significantly increased. After treatment with A. officinarum, the above indicators were improved in a dose-dependent manner. Through network pharmacology, 322 potential therapeutic targets of A. officinarum were screened out, and 12 core targets were further analyzed. Enrichment analysis showed that the mechanism of A. officinarum on SAKI mainly focused on signal transduction, apoptosis regulation, inflammation inhibition and hypoxia response. Molecular docking and kinetic simulation showed that the target EGFR had good binding stability with the active components ergocornine and 7, 2'-dihydroxyflavone. Conclusion A. officinarum can synergistically regulate multiple pathways through active ingredients and key targets, inhibit inflammatory response, improve renal function, and provide potential drugs and theoretical basis for the treatment of SAKI.
[中图分类号]
R285.5
[基金项目]
国家自然科学基金项目(82172175);东莞市社会发展科技项目(20221800906072); 2025年度大学生创新创业训练计划项目(S202512121111; S202512121113)