甘草酸二钾抑制组胺激活细胞以缓解气道高反应性OA
Dipotassium glycyrrhizinate inhibits histamine induced cell activation to alleviate airway hyperresponsiveness
研究拟建立组胺诱导的气道平滑肌细胞(ASMC)炎症模型,通过细胞活力实验、明胶酶谱法、细胞流式仪检测、蛋白质印迹分析和免疫荧光化学染色,研究甘草酸二钾(DG)对气道平滑肌细胞的作用,并探讨DG缓解气道高反应性的潜在药理机制.结果显示,DG通过抑制蛋白酶激活受体-2(PAR-2)/Toll样受体-4(TLR-4)/核因子-κB(NF-κB)信号通路和整联蛋白(Integrin-β1)/局部黏着斑激酶(FAK)信号通路来抑制组胺诱导的细胞增殖和迁移.DG通过上调抑癌基因(p53)、半胱氨酸天冬氨酸蛋白水解酶(Caspase3)、自噬效应蛋白(Beclin1)的表达和下调增殖细胞核抗原(PCNA)的表达,调节细胞周期,诱导过度活化的ASMC凋亡.通过分子对接模拟DG与组胺受体、PAR-2受体和TLR-4受体的结合,DG显示出较高的亲和力.研究表明DG可以抑制组胺诱导的ASMC过度激活和增殖,这为DG的多靶向调节提供了可能性,揭示了DG的抗组胺功能及其缓解气道高反应性的潜在药理学机制.
The study aims to establish a histamine-induced Airway Smooth Muscle Cells(ASMC)in-flammation model.Through cell viability assays,gelatin zymography,flow cytometry analysis,west-ern blot analysis,and immunofluorescence staining,the effects of Dipotassium Glycyrrhizinate(DG)on airway smooth muscle cells were investigated,and the potential pharmacological mechanism of DG in alleviating airway hyperresponsiveness was explored.The results showed that DG inhibited hista-mine-induced cell proliferation and migration by suppressing the Protease-Activated Receptor-2(PAR-2)/Toll-Like Receptor-4(TLR-4)/Nuclear Factor-kappa B(NF-κB)signaling pathway and the inte-grin-β1/Focal Adhesion Kinase(FAK)signaling pathway.DG regulated the cell cycle and induced ap-optosis of overactivated ASMC by upregulating the expression of tumor suppressor genes(p53),Cys-teine aspartate protease 3(Caspase3),and autophagy effector protein(Beclin1),and downregulating the expression of Proliferating Cell Nuclear Antigen(PCNA).Through molecular docking simula-tions,DG demonstrated high affinity for binding to histamine receptors,PAR-2 receptors,and TLR-4 receptors.The study indicates that DG can inhibit histamine-induced overactivation and proliferation of ASMC,and reveals the potential for multi-target regulation,unveiling DG's antihistamine function and its potential pharmacological mechanism in alleviating airway hyperresponsiveness.
练学娇;秦晶莹;周晓鹰
常州大学 药学院,江苏 常州 213164常州大学 药学院,江苏 常州 213164常州大学 药学院,江苏 常州 213164
医药卫生
气道平滑肌细胞组胺甘草酸二钾分子对接气道高反应性
airway smooth muscle cellshistaminedipotassium glycyrrhizinatemolecular dockingairway hyperresponsiveness
《常州大学学报(自然科学版)》 2026 (4)
61-72,12
江苏省研究生科研与实践创新计划资助项目(SJCX22_1317).
评论