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目的：基于网络药理学、分子对接技术探讨清心宁神汤治疗心不藏神不寐的作用机制，并进行实验验证。方法：采用中药系统药理学数据库分析平台对清心宁神汤的药物活性成分及其靶点进行检索，接着在disgenet、OMIM和GeneCards数据库中查询并筛选出与失眠相关的靶点。随后，构建蛋白相互作用网络数据库，并将药物与疾病相关的交集基因上传至DAVID数据库以进行KEGG和GO通路的富集分析，从而预测清心宁神汤治疗失眠的潜在作用靶点和信号通路。此外，对清心宁神汤的主要活性成分与核心靶点蛋白进行分子对接分析，并通过动物实验来验证这些活性成分与蛋白靶点对治疗心不藏神失眠大鼠模型的相关指标的影响。结果：在药物作用靶点与失眠相关靶点基因的交集分析中，共识别出181个同时与失眠和药物相关的靶点基因。其中AKT1、TNF、TP53、IL-6、IL-1β为核心靶点，GO分析共筛选条目1 052条，清心宁神汤治疗失眠富集的生物功能主要条目789条，细胞成分相关的有103条，分子功能相关的有160条；KEGG通路富集分析揭示了PI3K/AKT等170条信号通路的显著富集；而分子对接分析表明，AKT、NRF2、SOD等关键靶点与治疗失眠药物的亲和力较强。动物实验结果显示，清心宁神汤可改善GSH-Px、SOD及NRF2的表达，改善体内的氧化应激反应。结论：清心宁神汤能够通过作用于多个靶点和多条信号通路，对人体的氧化应激反应产生影响，从而改善GSH-Px、SOD及NRF2的表达水平，并调节PI3K/AKT信号通路中关键蛋白的表达，实现治疗心不藏神不寐的效果。
Abstract：Objective: To explore the mechanism of Qingxin Ningshen Decoction in the treatment of insomnia, and to carry out experimental verification, based on network pharmacology and molecular docking technology. Methods: The active ingredients and their targets of Qingxin Ningshen Decoction were searched using the TCM system pharmacology database analysis platform, and then the targets related to insomnia were screened in disgenet, OMIM, and GeneCards databases. Subsequently, the protein interaction network(PPI) database was constructed, and the intersection genes related to drugs and diseases were uploaded to the DAVID database for enrichment analysis of KEGG and GO pathways, so as to predict the potential targets and signaling pathways of Qingxin Ningshen Decoction in the treatment of insomnia. In addition, the molecular docking analysis of the main active components of Qingxin Ningshen Decoction and the core target protein was carried out, and the influence of these active components and protein targets on the related indexes of the treatment of insomnia rat model with cardiac failure was verified by animal experiments. Results: In the intersection analysis of drug action targets and insomnia related target genes, 181 target genes were identified. Among them, AKT1, TNF, TP53, IL-6, and IL-1β were the core targets. A total of 1 052 items were screened by GO analysis. There were 789 main items of biological function(BP), 103 related to cell components(CC), and 160 related to molecular function(MF) in Qingxin Ningshen Decoction for insomnia. KEGG pathway enrichment analysis revealed significant enrichment of 170 signaling pathways such as PI3K/AKT. Molecular docking analysis showed that AKT, NRF2, SOD and other key targets had a strong affinity with insomnia drugs. The results of animal experiments showed that Qingxin Ningshen decoction could improve the expression of GSH-Px, SOD and NRF2, and improve the oxidative stress reaction in vivo. Conclusion: Qingxin Ningshen Decoction can affect the oxidative stress response of human body by acting on multiple targets and multiple signaling pathways, thereby improving the expression levels of GSH-Px, SOD and NRF2, and regulating the expression of key proteins in PI3K/AKT signaling pathway, so as to achieve the effect of treating insomnia.
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基本信息:
DOI：10.13210/j.cnki.jhmu.20240924.001
中图分类号:R285
引用信息:
[1]吴金鸿,张星平,梁政亭,等.基于网络药理学、分子对接及实验验证探讨清心宁神汤治疗心不藏神不寐的作用机制[J].海南医科大学学报,2025,31(02):118-130.DOI:10.13210/j.cnki.jhmu.20240924.001.
基金信息:
国家自然科学基金资助项目（82160873,81960837,81560762,81260526）; 新疆维吾尔自治区自然科学基金资助项目（2022D01D48）; 国家中医药管理局“十四五”高水平中医药重点学科（国中医药人教函[2023]85号）; 全国名老中医药专家传承工作室（国中医药人教函[2022]75号）~~
2024-09-25
2024-09-25
2024-09-25