南京中医药大学学报2025，Vol.41Issue(9)：1148-1165,18.DOI:10.14148/j.issn.1672-0482.2025.1148
芪黄逐瘀方通过TNF信号通路减轻心肌梗死后抑郁的机制研究
Research on the Mechanism of Qihuang Zhuyu Formula in Alleviating Depression after Myocardial Infarction through the TNF Signaling Pathway
摘要
Abstract
OBJECTIVE To explore the mechanism of action of Qihuang Zhuyu formula(QHZYF)in improving depression after myocardial infarction(MI),with a focus on revealing its regulatory effect on the inflammatory response of the heart and brain.METH-ODS The active ingredients of QHZYF and the action targets for intervening in depression after MI were analyzed by using ultra-per-formance liquid chromatography-high-resolution mass spectrometry(UPLC-Q-TOF/MS)combined with network pharmacology and molecular docking.A rat model of depression after MI was established by ligation of the left anterior descending coronary artery com-bined with chronic restraint stress.Echocardiography was used to evaluate cardiac function,hematoxylin-eosin(HE)and Masson stai-ning were used to evaluate myocardial injury,behavioral tests were used to detect melancholic behaviors,Nissl staining was used to e-valuate hippocampal neuron injury.Western blot detection of tumor necrosis factor receptor 2(TNFR2),phosphatidylinositol-3-kinase(PI3K),phosphorylated seronine protein kinase(p-AKT),seronine protein kinase(AKT),tumor necrosis factor receptor 1(TNFR1),phosphorylated nuclear factor κB(p-NF-κB),and nuclear factor κB(NF-κB)in cardiac and hippocampal tissues was conducted.The levels of serum IL-6 and IL-10 were detected by enzyme-linked immunosorbent assay(ELISA),and the expression of TNFR1 and TNFR2 was detected by immunohistochemical technique(IHC).In vitro experiments,co-culture of rat cardiomyocyte line H9C2 cells and rat adrenal pheochromocytoma cell line with high differentiation PC12 cells was conducted,TNFR1 inhibitor(H398)and TNFR2 agonist(C-6His)were administered for intervention,and the expression of TNFR2,PI3K,p-AKT,AKT,TN-FR1,NF-κB,p-NF-κB was detected by Western blot.Observe the apoptosis of cells by TUNEL staining,ELISA was used to detect the levels of IL-6 and IL-10 in the cell supernatant.RESULTS Network pharmacological analysis indicates that the TNF signaling pathway was a key target for the treatment of depression after MI with the QHZYF.In vivo experiments have confirmed that the interven-tion of QHZYF could significantly improve the cardiac function,myocardial tissue and hippocampal neuron structure damage of de-pressed rats after MI,and improve their depression-like behaviors.At the molecular level,the high-dose group of QHZYF significant-ly upregulated TNFR2,p-AKT/AKT,and IL-10 in cardiac and hippocampal tissues(P＜0.01),and downregulated TNFR1,p-NF-κB/NF-κB and IL-6(P＜0.01).In vitro experiments showed that the drug-containing serum of QHZYF significantly upregulated the expression of TNFR2,p-AKT/AKT and IL-10 in H9C2 and PC12 cells(P＜0.01),downregulated the expression of TNFR1,p-NF-κB/NF-κB and IL-6(P＜0.01),and significantly inhibited cell apoptosis(P＜0.01).Furthermore,experiments on the combined ap-plication of H398 or C-6His further confirmed that its protective and anti-inflammatory effects were mediated by regulating the TN-FR2/PI3K/AKT and TNFR1/NF-κB pathways.CONCLUSION QHZYF improves the homeostasis of heart and brain inflammation by regulating the TNF pathway,and ameliorates myocardial injury and depressive state in depressed rats after MI.关键词
心肌梗死/抑郁/炎症/芪黄逐瘀方Key words
myocardial infarction/depression/inflammation/Qihuang Zhuyu formula分类
医药卫生引用本文复制引用
李江红,孙彤,俞鹏,沈乐,孙伟新,陈晓虎..芪黄逐瘀方通过TNF信号通路减轻心肌梗死后抑郁的机制研究[J].南京中医药大学学报,2025,41(9):1148-1165,18.基金项目
国家自然科学基金面上项目(81973824) （81973824）
国家自然科学基金青年科学基金项目(82205028) （82205028）
江苏省中医药管理局项目(k2021j17-2) （k2021j17-2）
江苏省中医院项目(y2021rc06) （y2021rc06）
江苏省中医药科技发展规划项目(QN202118) （QN202118）
江苏省中西医结合协会青年科技人才支持项目(JSZXTJ-2024-B05) （JSZXTJ-2024-B05）
江苏省青年科技人才支持项目(JSTJ-2024-577) （JSTJ-2024-577）
