摘要
目的 利用网络药理学方法和实验验证探讨黄芩改善手术患者术后认知功能障碍的作用机制。方法 采用网络药理学方法筛选黄芩作用于术后认知功能障碍的相关靶点及通路,再通过分子对接验证核心成分与关键靶点的亲和力。培养小鼠海马神经元HT22细胞系,应用LPS刺激细胞产生炎症损伤,选取黄芩素进行干预治疗,分为对照组、模型组、黄芩素低剂量组(10μmol/L)、黄芩素中剂量组(50μmol/L)和黄芩素高剂量(100μmol/L)组共5组。共培养24 h后,通过Western bolt检测关键靶点蛋白HIF1A、MAPK1(ERK2/p-ERK2)、SIRT1的表达,qRT-PCR检测以上蛋白mRNA表达。结果 网络药理学方法共筛选得到黄芩27个活性成分,对应379个靶点,POCD对应疾病靶点220个,两者取交集后共有35个交集靶点。分子对接结果显示黄芩素、山姜素等与HIF1A、MAPK1、SIRT1等靶点有较强亲和力。体外实验结果显示,黄芩素可明显下调HIF1A、MAPK1(ERK2/p-ERK2)蛋白表达和转录水平,同时上调SIRT1蛋白表达和转录水平,从而有效改善HT22细胞炎症反应,减少神经元损害。结论 中药黄芩可通过改善关键蛋白表达,控制炎症反应,保护神经元功能,降低术后认知功能障碍的发生与发展。
Objective To explore the mechanism of Scutellaria baicalensis(Huangqin)in ameliorating postoperative cognitive dysfunction in surgical patients through network pharmacology approaches combined with experimental validation.Methods Network pharmacology was used to screen the relevant targets and pathways of Huangqin in relation to postoperative cognitive dysfunction,followed by molecular docking to verify the affinity of core components with key targets.HT22 cell line of mouse hippocampal neurons was cultured,and an inflammation injury model was induced by LPS stimulation.Huangqin was selected for intervention treatment,divided into five groups:control group,model group,low-dose Huangqin group(10µmol/L),medium-dose Huangqin group(50µmol/L),and high-dose Huangqin group(100µmol/L).After co-culturing for 24 h,the expression of key target proteins HIF1A,MAPK1(ERK2/p-ERK2),and SIRT1 were detected by Western blotting,and the mRNA expression of these proteins was measured by qRT-PCR.Results A total of 27 active components of Huangqin were screened by network pharmacology,corresponding to 379 targets,with 220 disease targets related to POCD,resulting in 35 intersecting genes.Molecular docking results showed that components like baicalein and oroxylin A had strong affinity with targets such as HIF1A,MAPK1,and SIRT1.In vitro experimental results indicated that baicalein significantly downregulated the expression and transcription levels of HIF1A and MAPK1(ERK2/p-ERK2),while upregulating the expression and transcription levels of SIRT1,effectively improved the inflammatory response in HT22 cells and reduced neuronal damage.Conclusion The traditional Chinese medicine Huangqin can reduce the occurrence and development of postoperative cognitive dysfunction by improving the expression of key proteins,controlling inflammatory responses,and protecting neuronal function.
作者
李荣华
蔡靓羽
徐永成
刘砂金
王敬格
薛傲
徐敏逸
LI Ronghua;CAI Liangyu;XU Yongcheng;LIU Shajin;WANG Jingge;XUE Ao;XU Minyi(Wuxi Affiliated Hospital of Nanjing University of Chinese Medicine,Wuxi 214071,China;Nanjing University of Chinese Medicine,Graduate School,Nanjing 210023,China;Traditional Chinese Medicine Degenerative Osteoarthritis Clinical Innovation Center of Jiangsu Province,Wuxi 214071,China)
出处
《世界科学技术-中医药现代化》
北大核心
2025年第8期2406-2417,共12页
Modernization of Traditional Chinese Medicine and Materia Medica-World Science and Technology
基金
江苏省中医药管理局科研项目(MS2022057):黄芩苷介导ERK/CREB信号在老年POCD中发挥神经保护作用的研究,负责人:蔡靓羽
南京中医药大学自然科学基金项目(XZR2023025):黄芩苷改善老年骨折术后认知功能障碍的机制研究,负责人:蔡靓羽
无锡市卫生健康委员会科研项目(Q202260):基于脑-肠轴理论探究电针疗法对老年患者围术期神经认知障碍的临床疗效及作用机制,负责人:李荣华。
关键词
黄芩
术后认知功能障碍
网络药理学
分子对接
实验验证
分子机制
Huangqin
Postoperative cognitive dysfunction
Network pharmacology
Molecular docking
Experimental verification
Molecular mechanism
