姜黄素增强低糖低氧小胶质细胞M2极化的机制研究OACHSSCD
Mechanisms of Curcumin in Enhancing M2 Polarization of Microglia under Low-glucose and Hypoxic Culture Conditions
目的:初步探索姜黄素对低糖低氧培养的小胶质细胞M2极化及炎症介质表达的调控及可能机制.方法:构建小胶质细胞低糖低氧培养模型并检测姜黄素对不同低糖低氧培养时间的小胶质细胞炎症介质表达的影响.构建Toll样受体4(TLR4)基因干扰质粒并转染小胶质细胞,在低糖低氧培养18 h后检测Ml标志物和M2标志物的蛋白表达及炎症介质表达,还检测转录因子的蛋白表达.结果:在低糖低氧培养状态下姜黄素促进白细胞介素-4(IL-4)的表达,抑制炎症介质肿瘤坏死因子-α(TNF-α)、白细胞介素-1 β和白细胞介素-6的表达,同时姜黄素也显著抑制TLR4的表达.TLR4基因沉默进一步促进姜黄素诱导低糖低氧培养小胶质细胞M2极化,且进一步增强姜黄素对白细胞介素-4表达的促进作用及姜黄素对白细胞介素-1β表达的抑制作用.除此之外,姜黄素也显著抑制所测转录因子的蛋白表达,而且TLR4基因沉默可进一步增强姜黄素对所测转录因子蛋白表达的抑制作用.结论:在低糖低氧培养状态下姜黄素显著促进小胶质细胞M2极化,同时增强抑炎因子白细胞介素-4表达、抑制炎症介质白细胞介素-1R表达.
Objective:To preliminarily investigate the regulatory effects and possible mechanisms of curcumin on M2 polarization of microglia and inflammatory mediator expression under low-glucose and hypoxic culture conditions.Methods:A low-glucose and hy-poxia microglial culture model was established,and the effects of curcumin on inflammatory mediator expression in microglia under different durations of low-glucose and hypoxic culture were examined.A Toll-like receptor 4(TLR4)gene interference plasmid was constructed and transfected into microglia.After 18 hours of low-glucose and hypoxic culture,the protein expression of M1 and M2 markers,inflammatory mediators,and transcription factors was detected.Results:Under low-glucose and hypoxic culture conditions,curcumin promoted the expression of interleukin-4(IL-4)and inhibited the expression of inflammatory mediators tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1 β),and interleukin-6(IL-6).It also significantly suppressed TLR4 expression.TLR4 gene silencing further promoted curcumin-induced M2 polarization of microglia under low-glucose and hypoxia,and further enhanced the promoting effect of curcumin on IL-4 expression as well as its inhibitory effect on IL-1 β expression.In addition,curcumin signifi-cantly inhibited the protein expression of the detected transcription factors,and TLR4 gene silencing further enhanced its inhibitory effect on these transcription factors.Conclusion:Under low-glucose and hypoxic culture conditions,curcumin significantly promotes M2 polarization of microglia,enhances the expression of the anti-inflammatory factor IL-4,and inhibits the expression of the inflam-matory mediator IL-1β.
余美玲;李德跃;段炜
陆军军医大学第二附属医院神经内科,重庆,400037||川北医学院附属医院神经内科,南充,637000陆军军医大学第二附属医院药剂科,重庆,400037陆军军医大学第二附属医院神经内科,重庆,400037
医药卫生
慢性脑血流低灌注姜黄素小胶质细胞白细胞介素-4Toll样受体4炎症介质
Chronic cerebral hypoperfusionCurcuminMicrogliaInterleukin-4(IL-4)Toll-like receptor 4(TLR4)Inflamma-tory factors
《世界中医药》 2026 (4)
613-622,10
国家自然科学基金面上项目(81873757)重庆市自然科学基金项目(cstc2021jcyj-msxmX0494)重庆市中青年高端医学人才项目(2022CQ016).
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