Geniposide Reduces Inflammatory Responses of Oxygen-Glucose Deprived Rat Microglial Cells via Inhibition of the TLR4 Signaling Pathway
Geniposide Reduces Inflammatory Responses of Oxygen-Glucose Deprived Rat Microglial Cells via Inhibition of the TLR4 Signaling Pathway
复制标题
京尼平苷通过抑制 TLR4 信号通路减少缺氧-葡萄糖大鼠小胶质细胞的炎症反应
DOI：
10.1007/s11064-012-0852-8
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发表时间：
2012-10-01
影响因子：
4.4
通讯作者：
Liu, Jianxun
中科院分区：
文献类型：
--
作者：
Wang, Jun;Hou, Jincan;Liu, Jianxun
京尼平苷是从栀子中分离得到的一种环烯醚萜苷，具有抗氧化应激和抗炎的神经保护活性。本研究观察了京尼平苷对大脑中动脉阻塞(MCAO)大鼠脑缺血/再灌注损伤的体内保护作用，以及京尼平苷对体外缺氧缺糖(OGD)小胶质细胞活化的抑制作用及其机制。雄性SD大鼠于MCAO后即刻给予京尼平苷15、30、60 mg/kg治疗。观察再灌流24小时后脑梗塞体积和小胶质细胞活化情况。原代培养的大鼠小胶质细胞暴露于12.5、2 5和5 0μg/mL的京尼平苷，作用时间为4h。(2)培养上清中分泌肿瘤坏死因子-α、IL-1β、IL-6、IL-8和IL-10；(3)TLR4mRNA的表达；(4)TLR4、p-ERK1/2、p-IκB、p-p38的蛋白表达；核内和胞浆部分的NF-κB p65；(5)核转移核转录因子-κB p65。京尼平苷可缩小缺血半影区脑梗塞体积，抑制小胶质细胞活化。高糖饮食可增加细胞活力和释放肿瘤坏死因子α、白介素1β、白介素6、白介素8和白介素10，这些作用可被京尼平苷所抑制。京尼平苷还可减轻OGD诱导的TLR4mRNA和蛋白水平的升高。此外，25和50μg/mL京尼平苷可下调缺氧诱导的小胶质细胞ERK、IκB和p38的磷酸化，并抑制由NF-κB p65激活的核转录活性。结论：京尼平苷在体内对大鼠脑缺血再灌注损伤具有神经保护作用，在体外可通过抑制炎性因子和NF-κB的激活而抑制缺氧诱导的小胶质细胞活化。
Geniposide, an iridoid glycoside isolated from Gardenia, has neuroprotective activities against oxidative stress and inflammation. The present study investigated the in vivo protective effect of geniposide on ischemia/reperfusion-injured rats by middle cerebral artery occlusion (MCAO), and the inhibitory effects of geniposide and mechanisms against activation of microglial cells by oxygen-glucose deprivation (OGD) in vitro. Male SD rats were subjected to treatment with geniposide at 15, 30 and 60 mg/kg immediately after MCAO. Cerebral infarct volume and microglial cell activation were assessed following 24 h reperfusion. Cultured primary rat microglial cells were exposed to geniposide at the concentrations of 12.5, 25 and 50 μg/mL during 4 h of OGD. The effects of geniposide were evaluated in terms of (1) cell viability; (2) secretion of TNF-α, IL-1β, IL-6, IL-8 and IL-10 into culture media; (3)TLR4mRNA expression; (4) protein expression of TLR4, p-ERK1/2, p-IκB, p-p38, nuclear and cytoplasmic fraction NF-κB p65; and (5) nuclear transfer of NF-κB p65. Geniposide reduced the infarct volume and inhibited the activation of microglial cells in ischemic penumbra in vivo. OGD increased cell viability and release of TNF-α, IL-1β, IL-6, IL-8 and IL-10, these effects were suppressed by geniposide. Geniposide also attenuated the increases in the OGD-inducedTLR4mRNA and protein levels. In addition, geniposide at 25 and 50 μg/mL downregulated the phosphorylation of ERK, IκB and p38, as well as inhibited nuclear transcriptional activity triggered via NF-κB p65 in microglial cells by OGD. In conclusion, geniposide displays a neuroprotective effect on ischemia/reperfusion-injured rats in vivo and inhibits OGD-induced activation of microglial cells by attenuating inflammatory factors and NF-κB activation in vitro.