摘要
目的探讨姜黄素对脂多糖(LPS)诱导的小胶质细胞(MG)炎症反应的抑制作用,并观察上述作用是否通过髓样细胞触发受体2(TREM2)和Toll样受体4(TLR4)分子介导。方法建立LPS诱导BV-2小胶质细胞活化神经系统炎症模型,分为:对照组、LPS组、姜黄素处理组,姜黄素处理组按姜黄素不同浓度再分为3个姜黄素低剂量亚组(1、5和10μmol·L^-1亚组)和2个姜黄素高剂量亚组(20和40μmol·L^-1亚组)。倒置相差显微镜观察小胶质细胞形态变化,CCK-8法检测各组细胞活性,qRT-PCR法检测促炎因子白细胞介素-1β(IL-1β)和IL-6,抗炎因子IL-4和精氨酸酶1(Arg-1);Western blot检测TREM2和TLR4蛋白表达水平。结果姜黄素低剂量亚组对小胶质细胞活性无明显影响,差异无统计学意义(P> 0.05);姜黄素高剂量亚组小胶质细胞活性显著抑制,差异有统计学意义(P <0.05)。与LPS组比较,姜黄素处理组LPS诱导的小胶质细胞形态变化及促炎因子IL-1β和IL-6转录水平显著抑制(P <0.05),抗炎因子IL-4和Arg-1转录水平显著增加;TLR4表达水平显著降低(P <0.05);TREM2表达水平显著增加(P <0.05)。结论姜黄素可调控LPS诱导的小胶质细胞炎症反应表型,可能通过TREM2-TLR4分子介导发挥作用。
Aim To investigate the inhibitory effect of curcumin on lipopolysaccharide( LPS)-induced microglia( MG) inflammatory response,and whether the above effects were mediated by myeloid celltriggering receptor 2( TREM2) and Toll-like receptor 4( TLR4).Methods LPS induced BV-2 microglial activation of nervous system inflammation model was established,which was divided into a control group,a LPS group,three curcumin low dose groups( 1,5 and 10 μmol·L^-1) and two curcumin high dose groups( 20 and 40 μmol·L^-1).The morphology of microglia was observed by inverted phase contrast microscope.The cell viability was detected by CCK-8 method.The pro-inflammatory factors interleukin-1β( IL-1β) and IL-6 and anti-inflammatory factors IL-4 and arginase 1( Arg-1) were detected by qRT-PCR.TREM2 and TLR4 protein expression levels were detected by Western blot analysis.Results The low dose of curcumin had no significant effect on the cell viability of microglia,and the difference was not statistically significant( P > 0.05).The cell viability of microglia in the high dose group was significantly inhibited( P < 0.05).Compared with the LPS group,curcumin pretreated reversed the LPS-induced microglia morphological changes and the pro-inflammatory factors IL-1β and IL-6 transcription levels were significantly inhibited( P < 0.05),and the anti-inflammatory factors IL-4 and Arg-1 were significantly increased;TLR4 protein expression level was significantly decreased( P < 0.05);TREM2 protein expression level was significantly increased( P < 0.05).Conclusion Curcumin can regulate microglial inflammatory phenotype in LPS-induced BV2 cell which may be mediated through TREM2-TLR4.
作者
张嘉维
郑亚玲
罗燕
张晓洁
付剑亮
ZHANG Jia-wei;ZHENG Ya-ling;LUO Yan;ZHANG Xiao-ie;FU Jian-liang(Department of Neurology,the Sixth People's Hospital Affiliated to Shanghai Jiaotong University,Shanghai 200233,China)
出处
《中国临床神经科学》
2019年第4期386-394,共9页
Chinese Journal of Clinical Neurosciences
基金
国家自然科学基金(编号:81871103,81672243)
