铜纳米颗粒对缺血性卒中后神经血管单元的保护作用

Protective Effects of Copper Nanoparticles Against the Neurovascular Unit after Ischemic Stroke

目的:研究铜纳米颗粒(copper nanoparticle, Cu-nps)对缺血性卒中后神经血管单元(neurovascular units, NVU)的保护作用。方法:采用加热搅拌法合成Cu-nps。体内建立大鼠短暂大脑中动脉阻塞/再灌注模型(transient middle cerebral artery occlusion/reperfusion, tMCAO),实验分为正常组(sham)、模型组(tMCAO)、给药组(Cu-nps),检测各组脑梗死面积、神经凋亡情况、血脑屏障(blood-brain barrier, BBB)完整性以及相关蛋白表达。结果:制备出的Cu-nps以Cu2+、80 nm左右的粒径均匀存在,具有良好的生物相容性。Cu-nps靶向脑缺血部位受损神经元,提高神经元细胞活力,降低活性氧,减少神经元凋亡和脑梗死面积,降低伊文思蓝染料渗漏量和炎症因子表达。结论:Cu-nps可以减少氧化应激,保护BBB完整性,降低神经胶质细胞活化,保护NVU功能,从而降低脑缺血再灌注损伤。

Objective: To study the protective effect of copper nanoparticles(Cu-nps) on the neurovascular units(NVU) after ischemic stroke. Methods: Cu-nps was synthesized by heating and stirring method. A model of rat transient middle cerebral artery occlusion/reperfusion(tMCAO) was established in vivo. The experiment was divided into three groups, including normal group(Sham), model group(tMCAO), and dosing group(Cu-nps). Brain infarction area, neural apoptosis, blood-brain barrier(BBB) integrity, and related protein expression were detected in each group. Results: Cu-nps were successfully prepared and present in the form of Cu2+with a uniform particle size around 80 nm and good biocompatibility. Cu-nps target damaged neurons in cerebral ischemia, improve neuronal cell viability, reduce reactive oxygen species(ROS), reduce neuronal apoptosis and cerebral infarct area, and reduce EB dye leakage and inflammatory cytokine expression. Conclusion: Cu-nps reduce cerebral ischemia-reperfusion injury, protect BBB integrity, reduce oxidative stress, protect NVU function and therefore reduce glial cell activation.