Baicalin attenuates proinflammatory cytokine production in oxygen-glucose deprived challenged rat microglial cells by inhibiting TLR4 signaling pathway
Baicalin attenuates proinflammatory cytokine production in oxygen-glucose deprived challenged rat microglial cells by inhibiting TLR4 signaling pathway
复制标题
黄芩苷通过抑制 TLR4 信号通路，减弱氧糖剥夺攻击大鼠小胶质细胞中促炎细胞因子的产生
DOI：
10.1016/j.intimp.2012.10.013
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发表时间：
2012-12-01
影响因子：
5.6
通讯作者：
Liu, Jianxun
中科院分区：
文献类型：
--
作者：
Hou, Jincai;Wang, Jun;Liu, Jianxun
黄芩苷是从黄芪中分离得到的黄酮类化合物，具有多种药理作用。本研究旨在观察黄芩苷对氧糖剥夺（OGD）诱导的小胶质细胞活化的抑制作用及其机制。培养的大鼠原代小胶质细胞暴露于黄芩苷在10 μ g/ml，20 μ g/ml和40 μ g/ml的终浓度在4小时的OGD。黄芩苷对（i）细胞活力;（ii）促炎细胞因子分泌;（iii）TIr 4 mRNA表达;（iv）p-c-jun、p-ERK 1/2、p-INK、p-p38、TRAF 6和p-I κ B-α水平的影响;和（v）使用细胞计数试剂盒-8（CCK-8），酶联免疫吸附测定（ELISA），逆转录-聚合酶链反应（RT-PCR）、免疫印迹和免疫荧光双标染色。OGD增加细胞活力和TNF-α，IL-1 β，IL-6和IL-8的释放，这些作用被黄芩苷抑制。黄芩苷还减弱了OGD诱导的Tlr 4 mRNA表达的增加。此外，高剂量黄芩苷可显著降低TRAF 6水平。黄芩苷还能下调小胶质细胞I kappa B-α、c-jun、ERK 1/2、JNK、p38的磷酸化，抑制OGD诱导的MyD 88由胞浆向胞膜的转移。结果表明黄芩苷可通过抑制炎症因子和调节TLR 4信号通路抑制OGD诱导的小胶质细胞炎症因子的产生。(C)2012爱思唯尔有限公司版权所有。
Baicalin, a flavonoid compound isolated from Scutellariae radix, has been shown to possess a number of pharmacological effects. The aim of the present study was to observe the inhibitory effects of baicalin on the activation of microglial cells induced by oxygen-glucose deprivation (OGD) and the specific mechanisms by which these effects are mediated. Cultured rat primary microglial cells were exposed to baicalin at final concentrations of 10 mu g/ml, 20 mu g/ml and 40 mu g/ml during 4 h of OGD. The effects of baicalin on (i) cell viability; (ii) secretion of proinflammatory cytokines; (iii) TIr4 mRNA expression; (iv) p-c-jun, p-ERK1/2, p-INK, p-p38, TRAF6 and p-I kappa B-alpha levels; and (v) co-localization of TLR4 and MyD88 were evaluated using the Cell Counting Kit-8 (CCK-8), enzyme-linked immunosorbent assays (ELISA), reverse transcription-polymerase chain reaction (RT-PCR), western blot and double-labeled immunofluorescence staining, respectively. OGD increased cell viability and release of TNF-alpha, IL-1 beta, IL-6 and IL-8, these effects were suppressed by baicalin. Baicalin also attenuated the OGD-induced increases in Tlr4 mRNA expression. In addition, high dose of baicalin reduced TRAF6 levels remarkably. Furthermore, baicalin also downregulated phosphotylation of I kappa B-alpha, c-jun, ERK1/2, JNK, p38 and inhibited the OGD-induced transfer of MyD88 from cytoplasm to membrane in microglial cells. The results show that baicalin can inhibit OGD-induced production of inflammatory factors in microglial cells by attenuating inflammatory factors and regulating the TLR4 signaling pathways. (C) 2012 Elsevier B.V. All rights reserved.