基于网络药理学验证速效救心丸通过PI3K/AKT/GSK3B/β-catenin通路促进心肌修复的机制OA
Network-based pharmacological validation of the mechanism by which Suxiao Jiuxin pill promote myocardial repair via the PI3K/AKT/GSK3B/β-catenin signaling pathway
目的 运用网络药理学预测速效救心丸促进心肌细胞增殖的有效成分、靶点及相关通路,并通过体外细胞实验验证其分子机制.方法 通过中药系统药理数据库(TCMSP)筛选速效救心丸的有效成分,PubChem 数据库、SwissTargetPrediction 数据库寻找相关靶点;在 OMIM 数据库和 GeneCards 数据库获取细胞增殖相关靶点;借助 Metascape 数据库进行 KEGG 通路和 GO 功能富集分析.并进行体外实验验证,以 HL-1 心肌细胞为研究对象,CCK-8 法确定细胞活性及速效救心丸最佳浓度;Western blot 检测 HIF-1α 水平;EdU 掺入实验检验缺氧后 HL-1心肌细胞的增殖水平;Western blot 检测通路标志物的表达水平;AutoDock 对核心蛋白和关键小分子进行分子对接预测分子-靶点配对.结果 本研究共筛选速效救心丸符合条件的成分39 种,其中 33 种来自川芎,6 种来自冰片;药物疾病关键靶点 238 个;GO 分子功能 359 种,KEGG 通路富集 212 条.CCK-8实验结果显示在速效救心丸浓度为 10 μg/mL 时增殖效果最佳;缺氧最佳时间为 24 h;与缺氧组相比,速效救心丸组细胞中的 p-PI3K、p-AKT、p-GSK3B、β-catenin 相对表达升高(P<0.05,P<0.01);杨梅酮-MAPK3显示出较好的结合活性.结论 速效救心丸可通过激活PI3K/AKT/GSK3B/β-catenin 通路调控急性心肌梗死后心肌增殖促进心肌修复.
Objective To predict the active ingredients,molecular targets,and signaling pathways through which Suxiao Jiuxin pill(SJP)promote cardiomyocyte proliferation using network pharmacology,and to validate the underlying molecular mechanisms in vitro.Methods Active compounds were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and their molecular targets were retrieved from the PubChem and SwissTargetPrediction databases.Cardiomyocyte proliferation-related targets were sourced from OMIM and GeneCards databases.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were conducted using Metascape.Experimental validation was conducted in HL-1 cardiomyocytes.Cell viability and the optimal SJP concentration were assessed using the Cell Counting Kit-8 assay.Cardiomyocyte proliferation after hypoxia was evaluated by 5-ethynyl-2'-deoxyuridine(EdU)incorporation.Protein expression of hypoxia-inducible factor-1α(HIF-1α)and key signaling molecules was analyzed by Western blot.Molecular docking between core proteins and key compounds was performed using AutoDock.Results Thirty-nine bioactive compounds were identified in SJP(33 from Chuanxiong Rhizoma,6 from Borneol),along with 238 key drug-disease targets.GO enrichment identified 359 molecular functions,and KEGG analysis identified 212 signaling pathways.SJP at 10 μg/mL produced the strongest proliferative effect,with an optimal hypoxia duration of 24 h.Compared with hypoxia group,SJP treatment significantly increased the relative expression levels of phosphorylated(p)-phosphatidylinositol 3-kinase(p-PI3K),p-protein kinase B(p-AKT),p-glycogen synthase kinase 3-beta(GSK3β),and β-catenin(P<0.05,P<0.01).Molecular docking demonstrated strong binding affinity between myricanone and mitogen-activated protein kinase 3.Conclusions SJP may promote post-infarction myocardial repair by enhancing cardiomyocyte proliferation through activation of the PI3K/AKT/GSK3β/β-catenin signaling pathway.
黄程新;阮小芬;王肖龙;李琳;刘洁;孙元隆
上海中医药大学附属曙光医院 心血管病研究室,上海 201203上海中医药大学附属曙光医院 心血管病研究室,上海 201203||上海中医药大学附属曙光医院 国家中医心血管病临床医学研究中心分中心,上海 201203上海中医药大学附属曙光医院 心血管病研究室,上海 201203||上海中医药大学附属曙光医院 国家中医心血管病临床医学研究中心分中心,上海 201203上海中医药大学附属曙光医院 心血管病研究室,上海 201203上海中医药大学附属曙光医院 国家中医心血管病临床医学研究中心分中心,上海 201203上海中医药大学附属曙光医院 心血管病研究室,上海 201203
医药卫生
急性心肌梗死速效救心丸PI3K/AKT/GSK3B/β-catenin心肌修复网络药理学
acute myocardial infarctionSuxiao Jiuxin pillPI3K/AKT/GSK3B/β-cateninmyocardial repairnetwork pharmacology
《中国比较医学杂志》 2026 (16)
40-52,13
国家自然科学基金面上项目(8217415282608587)上海中医药大学附属曙光医院四明基金(SGKJ-202507).
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