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中国生物工程杂志

CHINA BIOTECHNOLOGY
中国生物工程杂志  2022, Vol. 42 Issue (12): 1-11    DOI: 10.13523/j.cb.2207022
研究报告     
铜纳米颗粒对缺血性卒中后神经血管单元的保护作用
黄纪安,李婉萌,刘薇,齐梓彤,赵亮()
锦州医科大学药学院 锦州 121001
Protective Effects of Copper Nanoparticles Against the Neurovascular Unit after Ischemic Stroke
HUANG Ji-an,LI Wan-meng,LIU Wei,QI Zi-tong,ZHAO Liang()
School of Pharmacy, Jinzhou Medical University, Jinzhou 121001, China
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摘要:

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。

关键词: 铜纳米颗粒缺血性卒中神经血管单元再灌注损伤    
Abstract:

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.

Key words: Copper nanoparticles    Ischemic stroke    Neurovascular unit    Ischemia-reperfusion injury
收稿日期: 2022-07-13 出版日期: 2023-01-05
ZTFLH:  R94  
通讯作者: 赵亮     E-mail: liangzhao79@163.com
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黄纪安
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引用本文:

黄纪安,李婉萌,刘薇,齐梓彤,赵亮. 铜纳米颗粒对缺血性卒中后神经血管单元的保护作用[J]. 中国生物工程杂志, 2022, 42(12): 1-11.

HUANG Ji-an,LI Wan-meng,LIU Wei,QI Zi-tong,ZHAO Liang. Protective Effects of Copper Nanoparticles Against the Neurovascular Unit after Ischemic Stroke. China Biotechnology, 2022, 42(12): 1-11.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/10.13523/j.cb.2207022        https://manu60.magtech.com.cn/biotech/CN/Y2022/V42/I12/1

图1  Cu-nps的形态和结构表征
图2  Cu-nps可逆转OGD诱导的tMCAO大鼠神经元损伤
图3  Cu-nps通过促进紧密连接蛋白的升高来保护血脑屏障
图4  Cu-nps的生物相容性评价
Number 1 2 3 4 5 6
2% Red blood cell solution /mL 2.5 2.5 2.5 2.5 2.5 2.5
Normal saline /mL - 2.5 0.5 1.5 2 2.25
Distilled water /mL 2.5 - - - - -
Cu-nps /mL - - 2 1 0.5 0.25
表1  Cu-nps材料、质量分数为2%红细胞悬液、生理盐水的配比
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