Ginkgolide B Protects Against Ischemic Stroke Via Modulating Microglia Polarization in Mice
Ginkgolide B Protects Against Ischemic Stroke Via Modulating Microglia Polarization in Mice
复制标题
银杏内酯 B 通过调节小鼠小胶质细胞极化来预防缺血性中风
DOI：
10.1111/cns.12577
复制
发表时间：
2016-09-01
影响因子：
5.5
通讯作者：
Hu, Gang
中科院分区：
文献类型：
--
作者：
Shu, Zhao-Ma;Shu, Xiao-Dong;Hu, Gang
AimGinkgolide B （GB）在缺血性脑卒中治疗中显示出神经保护作用，这与其抗炎作用有关。然而，目前尚不清楚GB是否能够调节小胶质细胞/巨噬细胞极化，这在缺血性卒中的病理中最近被证明是至关重要的。方法对C57BL/6J雄性小鼠进行短暂性大脑中动脉闭塞（tMCAO）， LPS+干扰素-和IL-4诱导培养的BV2小胶质细胞和原代骨髓源性巨噬细胞分别为M1/2表型。采用免疫荧光和流式细胞术检测M1/2特异性蛋白CD206、CD16/32的表达。采用qPCR检测M1/2的特征基因变化。结果葛根素能明显减轻小鼠脑缺血损伤，改善小鼠神经功能缺损。更重要的是，我们的实验证明，在体内或体外，GB促进小胶质细胞/巨噬细胞从炎性M1表型向保护性、抗炎的M2表型转移。CV3988和siRNA沉默血小板激活因子（PAF）受体表明，PAF受体参与了小胶质细胞/巨噬细胞极化的调节。ConclusionOur结果揭示小说GB的药理效应调制tMCAO后小胶质细胞/巨噬细胞极化,从而深化我们对神经保护机制的理解GB治疗缺血性中风。此外，这一新机制可能允许GB用于许多其他小胶质细胞/巨噬细胞极化相关的炎症性疾病。
AimGinkgolide B (GB) has shown neuroprotective effect in treating ischemic stroke, related to its property of anti-inflammation. Nevertheless, it is unclear whether GB is able to modulate microglia/macrophage polarization, which has recently been proven to be vital in the pathology of ischemic stroke.MethodsWe performed transient middle cerebral artery occlusion (tMCAO) on C57BL/6J male mice and induced cultured BV2 microglia and primary bone marrow-derived macrophages to be M1/2 phenotype by LPS+ interferon- and IL-4, respectively. Immunofluorescence and flow cytometry were used for detecting the specialized protein expression of M1/2, such as CD206 and CD16/32. qPCR was utilized to detect the signature gene change of M1/2.ResultsGB significantly reduced cerebral ischemic damage and ameliorated the neurological deficits of mice after tMCAO. More importantly, our experiments proved that GB promoted microglia/macrophage transferring from inflammatory M1 phenotype to a protective, anti-inflammatory M2 phenotype in vivo or vitro. CV3988 and silencing the platelet activator factor (PAF) receptor by siRNA demonstrated that PAF receptor was involved in the modulation of microglia/macrophage polarization.ConclusionOur results reveal a novel pharmacological effect of GB in modulating microglia/macrophage polarization after tMCAO, thus deepening our understanding of neuroprotective mechanisms of GB in treatment of ischemic stroke. Furthermore, this new mechanism may allow GB to be used in many other microglia/macrophage polarization-related inflammatory diseases.