异荭草苷调节小胶质细胞活化抑制内毒素血症小鼠神经炎症的研究

Isoorientin Regulates Microglia Activation to Inhibit Neuroinflammation in Endotoxemia Mice

目的研究异荭草苷(isoorientin,ISO)对内毒素血症小鼠神经炎症和小胶质细胞活化的干预作用及其对脑源性神经营养因子(BDNF)的影响。方法将BALB/c小鼠随机分为5组:空白对照组、脂多糖模型组(5 mg·kg^(-1),腹腔注射)、异荭草苷低剂量组(25 mg·kg^(-1),灌胃)、异荭草苷高剂量组(50 mg·kg^(-1),灌胃)、氯化锂组(100 mg·kg^(-1),灌胃)。定量RT-PCR或RT-PCR法检测小鼠肝脏和脾脏中白细胞介素(IL)-1β和肿瘤坏死因子α(TNF-α)水平以及脑皮质中诱导性一氧化氮合酶(iNOS)和精氨酸酶1(Arg^(-1))、细胞因子TNF-α和IL-1β的表达水平。免疫荧光和蛋白印迹法检测皮质中离子钙结合衔接分子1(Iba1)以及BDNF的表达水平。结果异荭草苷可降低内毒素血症小鼠脾脏和肝脏中IL-1β和TNF-α的表达水平(P<0.05),同时异荭草苷还可减少脑组织中IL-1β、TNF-α、Iba1、iNOS和Arg^(-1)的表达水平(P<0.05),并且升高BDNF的表达(P<0.05)。结论异荭草苷能抑制内毒素血症小鼠外周及脑内炎症,通过抑制小胶质细胞活化、促进BDNF表达发挥神经保护作用。

Objective To investigate the interventional effect of isoorientin(ISO)on neuroinflammation,microglia activation and BDNF in endotoxemia mice.Methods BALB/c mice were randomly divided into 5 groups:control group,LPS model group(5 mg·kg^(-1),ip),isoorientin low dose group(25 mg·kg^(-1),ig),isoorientin high dose group(50 mg·kg^(-1),ig),lithium chloride group(100 mg·kg^(-1),ig).The levels of interleukin-1β(IL-1β)and tumor necrosis factor(TNF-α)in the liver and spleen,as well as the expression levels of inducible nitric oxide synthase(iNOS)and arginase-1(Arg^(-1)),cytokines TNF-αand IL-1βin the cortex were measured by RT-qPCR or RT-PCR.Then,the expressions of Ionized calcium binding adapter molecule 1(Iba1)and brain-derived neurotrophic factor(BDNF)in the cortex were measured by immunofluorescence and Western Blotting.Results ISO treatment reduced the expression of IL-1βand TNF-αin the spleen and liver of endotoxemia mice(P<0.05).And ISO also reduced the expression of IL-1β,TNF-α,Iba1,iNOS and Arg^(-1) in brain(P<0.05),while it increased the expression of BDNF(P<0.05).Conclusion ISO can inhibit peripheral and brain inflammation,inhibit microglia activation and increase BDNF to exert neuroprotective effects in endotoxemia mice.