摘要
目的研究异甘草素对血管内皮细胞炎症反应的保护作用,以及异甘草素是否通过组蛋白去乙酰化酶3(histone deacetylase 3,HDAC3)调控血管内皮细胞的炎症反应。方法以人脐静脉内皮细胞(HUVECs)为研究对象,分别给予脂多糖(LPS)刺激、不同浓度异甘草素联合LPS处理细胞、HDAC3特异性抑制剂和异甘草素联合LPS处理细胞,Real-time PCR和Western blotting检测细胞炎症因子和HDAC3的mRNA和蛋白表达。雄性C57BL/6J小鼠随机分为溶剂对照组和异甘草素组,颈动脉结扎手术建立小鼠急性血管炎症模型,Real-time PCR检测小鼠颈动脉炎症因子和HDAC3的mRNA表达。利用分子对接模型,从分子结构上揭示异甘草素和HDAC3之间的结合程度。结果与溶剂对照组相比,异甘草素组中LPS刺激所升高的血管内皮细胞炎症因子NLRP3、IL-1β、IL-18、MCP-1和ICAM-1的mRNA表达降低,细胞HDAC3的mRNA和蛋白表达降低。此外,颈动脉结扎的手术组小鼠中,异甘草素组的血管炎症因子NLRP3、IL-1β和HDAC3的mRNA表达降低。分子对接结果显示异甘草素与HDAC3之间具有结构上的契合性,而且HDAC3特异性抑制剂RGFP966能够进一步促进异甘草素对血管内皮细胞炎症因子表达的抑制作用。结论异甘草素可能通过HDAC3抑制血管内皮细胞的炎症反应。
Objective To investigate the effect of isoliquiritigenin on inflammatory response of vascular endothelial cells and whether the regulatory effect of isoliquiritigenin on inflammation is mediated by histone deacetylase 3(HDAC3).Methods Human umbilical vein endothelial cells(HUVECs)were cultured in vitro and treated with LPS,different concentrations of isoliquiritigenin and HDAC3 specific inhibitor,respectively.Real-time PCR and Western blotting were used to detect the mRNA and protein expressions of inflammatory cytokines and HDAC3.Male C57BL/6J mice were randomly divided into vehicle group and isoliquiritigenin treatment group.The vascular inflammation model of C57BL/6J mice was established by ligation of the left carotid arteries.The mRNA expressions of inflammatory cytokines and HDAC3 in the carotid arteries of mice were detected by Real-time PCR.A molecular docking study was performed to investigate the interaction between isoliquiritigenin and HDAC3.Results Compared with the vehicle group,isoliquiritigenin reduced the mRNA expressions of inflammatory cytokines NLRP3,IL-1β,IL-18,MCP-1 and ICAM-1 and decreased the expression of HDAC3 mRNA and protein in HUVECs stimulated with LPS.In addition,isoliquiritigenin also decreased the mRNA expressions of NLRP3,IL-1βand HDAC3 in carotid arteries of ligated C57BL/6J mice.The docking of isoliquiritigenin in the active site of HDAC3 showed that isoliquiritigenin might act through HDAC3.Furthermore,HDAC3 specific inhibitor RGFP966 further promoted the inhibitory effect of isoliquiritigenin on the expression of inflammatory cytokines in vascular endothelial cells.Conclusion These results suggest that isoliquiritigenin suppresses the inflammatory response of vascular endothelial cells via HDAC3.
作者
卢治言
李奕男
袁玥
马子阳
罗媛琳
陈力方
张艺蓉
王维蓉
LU Zhiyan;LI Yinan;YUAN Yue;MA Ziyang;LUO Yuanlin;CHEN Lifang;ZHANG Yirong;WANG Weirong(Department of Laboratory Animal Science,School of Basic Medical Science of Xi’an Jiaotong University Health Science Center,Xi’an 710061;Institute of Cardiovascular Science,Translational Medicine Institute,Xi’an Jiaotong University Health Science Center,Xi’an 710061,China)
出处
《西安交通大学学报（医学版）》
CAS
CSCD
北大核心
2023年第6期852-858,共7页
Journal of Xi’an Jiaotong University（Medical Sciences）
基金
国家自然科学基金资助项目(No.81873520)
陕西省创新能力支撑计划项目(No.2023-CX-PT-07)。
