原花青素抑制脂多糖激活神经小胶质细胞的机制  

Mechanism of proanthocyanidin-mediated inhibition of LPS-induced activation of microglial cells

作　　者：张妍[1,2] 张小强[1,2] 梁晓瑜[1,2] 王旭[1,2] 刘静[1,2] ZHANG Yan;ZHANG Xiaoqiang;LIANG Xiaoyu;WANG Xu;LIU Jing(School of Public Health,Southeast University,Nanjing 210009;Key Laboratory of Environmental Medicine,Engineering of Ministry of Education,Southeast University,Nanjing 210009,Jiangsu,China)

机构地区：[1]东南大学公共卫生学院,江苏南京210009 [2]东南大学环境医学工程教育部重点实验室,江苏南京210009

出　　处：《癌变．畸变．突变》2018年第2期98-102,共5页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金：中央高校基本科研业务费专项资金资助;江苏省普通高校研究生科研创新计划资助项目(SJZZ16_0034)

摘　　要：目的:研究原花青素抑制脂多糖(LPS)激活神经小胶质细胞的机制。方法:采用1.0μg/m L LPS刺激神经小胶质细胞建立体外炎症模型,再用不同浓度(0.1、0.5、2.5、10.0μg/m L)原花青素进行干预,四甲基噻唑蓝(MTT)法检测不同浓度原花青素对神经小胶质细胞的毒性,ELISA法检测炎症因子TNF-α、IL-1β、IL-6的表达,Western blot法检测TLR4、p38、p-p38蛋白的表达。结果:与对照组比较,1.0μg/m L LPS组TNF-α、IL-1β、IL-6水平均显著升高(P<0.05),TLR4和p-p38蛋白表达亦显著增加(P<0.05);给予不同浓度原花青素干预后,与1.0μg/m L LPS组比较,炎性因子TNF-α、IL-1β、IL-6分泌水平均下降(P均<0.05),TLR4和pp38蛋白表达水平均显著下调(P均<0.05)。结论:原花青素可能通过TLR4/p38 MAPK信号通路抑制脂多糖激活神经小胶质细胞。OBJECTIVE:The present study was designed to investigate the possible mechanisms of proanthocyanidin-mediated inhibition in lipopolysaccharide(LPS)-induced activation of microglial BV2 cells.METHODS:An inflammation cell model was produced in BV2 cells which were treated with LPS(1.0 g/mL).In addition,cells were treated with proanthocyanidins(0.1,0.5,2.5,10.0 g/mL)prior to LPS exposure and MTT assay was used to detect the viability of BV2 cells.The level of inflammatory cytokines TNF-,IL-1 and IL-6 were examined by ELISA method.TLR4 and p38,p-p38 MAPK protein expressions were examined by the Western blot analysis.RESULTS:Compared with the control group,LPS(1.0 g/mL)significantly increased the expression of TLR4 and p-p38 protein as well as the release of inflammatory mediator TNF-,IL-1 and IL-6(P<0.05).Proanthocyanidin significantly inhibited LPS-induced production of inflammatory mediators in a dose-dependent manner(P<0.05).Moreover,PC significantly inhibited the phosphorylation of p38 and TLR4 expression(P<0.05).CONCLUSION:Proanthocyanidin inhibited inflammatory mediator expression by suppressing TLR4 mediated p38 MAPK signaling pathways in LPS-stimulated BV2 cells.

关 键 词：原花青素 脂多糖 小胶质细胞 TLR4 P38 MAPK 

分 类 号：R994.6[医药卫生—毒理学]