乳铁蛋白修饰纳米粒包载的α-倒捻子素对AD模型动物脑内特征性病理改变的影响  

Effect of Lactoferrin Modified α-M Loaded Nanoparticle on the Pathological Changes in the Brain of an AD Animal Model

作　　者：侯丽娜[1] 谭小芳 倪雯雯[1] 邱瑜[1] 李娟[1] 

机构地区：[1]上海交通大学医学院药理学教研室,上海200025

出　　处：《现代生物医学进展》2017年第31期6046-6052,共7页Progress in Modern Biomedicine

基　　金：国家自然科学基金项目(81503044;81373417);上海市卫生局青年基金项目(20134Y174)

摘　　要：目的:采用乳铁蛋白修饰的PEG-PLA纳米粒为递药工具包载α-M,探讨其对快速老化SAMP8小鼠AD相关脑内病理特征的改善作用。方法:用乳化/溶剂蒸发法制备载α-M的PEG-PLA纳米粒NP(α-M),将巯基化的乳铁蛋白连接于纳米粒表面,得到Lf-NP(α-M)。7月龄SAMP8系小鼠尾静脉给予注射生理盐水、Lf-NP(α-M)或空白纳米粒溶液,每日一次,连续两周。正常老化小鼠SAMR为模型对照组,通过对脑组织进行免疫组化分析,观察Lf-NP(α-M)对SAMP8小鼠脑内炎症、Aβ沉积等AD特征性病理变化的影响。结果:0.5、2 mg/kgα-M对SAMP8小鼠脑内小胶质细胞激活、星形胶质细胞增生以及Aβ沉积均无显著影响;0.5mg/kg Lf-NP(α-M)可抑制小胶质细胞的激活(P<0.001),2 mg/m L Lf-NP(α-M)显著抑制星形胶质细胞增生以及Aβ沉积(P<0.05)。结论:乳铁蛋白修饰的包载α-M的可降解纳米粒脑靶向递药系统成功有效,显著提高α-M的成药性并改善AD模型小鼠脑内特征性病理改变。Objective： Lactoferrin was covalently conjugated to the α-M-loaded nanoparticles to receive Lf-NP（α-M）, the dis- ease modification effects of Lf-NP （α-M） in AD model mice was studied. Methods： α-M was loaded by poly （ethylene glycol）-poly（1-1actide） nanoparticles using emulsion/solvent evaporation method, and lactoferrin was covalently conjugated to it to form Lf-NP（α-M）. We adopt the normal aging mice SAMR as negative control to SAMP8 mice. Saline and blank nanoparticles or Lf-NP （α-M） were injected to SAMP8 mice once a day for two weeks through the tail vein. The Aβ deposition and neuroinflammatory responses in animal brain were assessed after that, to evaluated its disease modification effects in AD. Results： ct-M alone at 0.5 and 2 mg/kg could not significantly inhibit the activation of microglia, the proliferation ofastrocyte and the deposition of Aβ in the brain of SAMP8 mice. Lf-NP （α-M） could significantly attenuate the activation of the microglia 0.5 mg/kg （P〈0.001）, and the inhibiting effects of the proliferation ofastrocyte and the deposition of Aβ were significant at 2 mg/kg. Conclusions： Lf-NP （α-M） was a successful biodegradable and brain targeting drug delivering system, it could elevate the druggability of α-M, Lf-NP（α-M） could significantly improve the characterized pathological changes of AD in the brain of SAMP8 mice.

关 键 词：阿尔茨海默病 α-倒捻子素 纳米粒 乳铁蛋白 疾病修饰 

分 类 号：R-33[医药卫生] R741.02