栝楼桂枝汤通过抑制小胶质细胞活化改善大鼠脑缺血/再灌注损伤

GLGZD improves cerebral ischemia-reperfusioninjury in rats by inhibiting microglial activation

目的探讨栝楼桂枝汤(gua lou gui zhi decoction,GLGZD)是否通过影响脑缺血/再灌注损伤大鼠皮层小胶质细胞活化来发挥脑保护作用。方法采用线栓法制备大鼠大脑中动脉阻塞(MCAO)模型,GLGZD治疗7 d后,改良神经功能缺损评分评价各组大鼠的神经功能,小动物核磁共振检测大鼠脑梗死体积,TUNEL法检测缺血侧皮层神经细胞凋亡情况,免疫组化法检测缺血侧皮层脑组织中TNF-α蛋白的表达情况,RT-qPCR检测缺血侧皮层脑组织中神经元-小胶质细胞相互作用的相关因子TWEAK、Fn14、NIK、Rel B、CCL21、CXCR3 mRNA及小胶质细胞活化标志物IBA-1 mRNA表达情况。结果GLGZD能明显改善MCAO大鼠神经功能,显著减少MCAO大鼠脑梗死体积和缺血侧皮层神经细胞的凋亡;并可明显下调MCAO大鼠缺血侧皮层脑组织中TNF-α蛋白及TWEAK、Fn14、NIK、Rel B、CCL21、CXCR3、IBA-1 mRNA的表达。结论GLGZD能明显改善大鼠脑缺血/再灌注损伤,这一作用可能与其通过影响TWEAK/Fn14/CCL21/CXCR3信号通路抑制小胶质细胞活化有关。

Aim To study whether GLGZD exerts brain protection by affecting the activation of cortical microglia in cerebral ischemia-reperfusion rats.Methods The nylon thread plug was used to establish the MCAO model.After GLGZD treatment for seven days,mNSS was used to evaluate the neurological function of each group of rats,MRI to detect cerebral infarction volume in rats,TUNEL to detect the apoptotic rate of nerve cells,immunohistochemistry to detect TNF-αprotein expression in ischemic cortical brain tissues,and RT-qPCR to detect mRNA expression of neuron-microglia interaction-related factors TWEAK,Fn14,NIK,Rel B,CCL21,CXCR3 and microglial activation marker IBA-1 in ischemic cortical brain tissues.Results GLGZD could significantly improve the neurological function of MCAO rats,and markedly reduce the infarct volume and apoptosis of ischemic cortical neurons in MCAO rats.It also could significantly down-regulate the expressions of TNF-αprotein and TWEAK,Fn14,NIK,Rel B,CCL21,CXCR3 and IBA-1 mRNA in ischemic cortex of MCAO rats.Conclusions GLGZD can significantly improve cerebral ischemia-reperfusion injury in rats,which may be related to inhibition of microglial cell activation by affecting TWEAK/Fn14/CCL21/CXCR3 signaling pathway.