| 侯丽娜,谭小芳,倪雯雯,邱 瑜,李 娟.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[J].,2017,17(31):6046-6052 |
| 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 |
| 投稿时间：2017-06-29 修订日期：2017-07-17 |
| DOI：10.13241/j.cnki.pmb.2017.31.011 |
| 中文关键词: 阿尔茨海默病 α-倒捻子素 纳米粒 乳铁蛋白 疾病修饰 |
| 英文关键词: Alzheimer's disease α-mangostin Nanoparticle Lactoferrin Disease modification |
| 基金项目: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） |
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| 中文摘要: |
| 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/kg α-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；0.5 mg/kg Lf-NP(α-M)可抑制小胶质细胞的激活(P<0.001)，2 mg/mL 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。 |
| 英文摘要: |
| ABSTRACT 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(l-lactide) 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: α-M alone at 0.5 and 2 mg/kg could not significantly in- hibit the activation of microglia, the proliferation of astrocyte 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 of astrocyte and the deposition of Aβ were significant at 2 mg/kg. Conclusion: Lf-NP(α-M) was a successful biodegradable and brain targeting drug de- livering 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. |
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