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载姜黄素纳米铁蛋白递药系统通过血脑屏障并减轻 D-半乳糖诱导的小鼠神经退行性变。

LYC loaded ferritin nanoparticles for intracerebral delivery and the attenuation of neurodegeneration in D-gal-induced mice.

机构信息

School of Food Science and Technology, National Engineering Research Center of Seafood, Dalian Polytechnic University, Dalian 116034, China.

School of Food Science and Technology, National Engineering Research Center of Seafood, Dalian Polytechnic University, Dalian 116034, China.

出版信息

Biomater Adv. 2023 Aug;151:213419. doi: 10.1016/j.bioadv.2023.213419. Epub 2023 Apr 5.

DOI:10.1016/j.bioadv.2023.213419
PMID:37148595
Abstract

Recombinant human H-ferritin nanocage (rHuHF) loaded with natural antioxidative lycopene molecules (LYC) was successfully constructed for the first time, aiming to enrich LYC in the brain and explore the regulation mechanism of this nanoparticles on neurodegeneration. Here, the mouse model was constructed via D-galactose-induced neurodegeneration based on behavioural analysis, histological observation, immunostaining analysis, Fourier transform infrared microscopy, and Western blotting analysis for the regulation of rHuHF-LYC. rHuHF-LYC improved the behaviour of mice in a dose-dependent manner. Besides, rHuHF-LYC can attenuate neuronal damage, maintain the number of Nissl body, increase the level of unsaturated fat, inhibit the activation of glial cells, and prevent excessive accumulation of neurotoxic proteins in the hippocampus of mice. More importantly, synaptic plasticity was activated in response to the regulation of rHuHF-LYC with excellent biocompatibility and biosafety. This study proved the validity of the direct use of natural antioxidant nano drugs for treating neurodegeneration, providing a promising therapeutic option against further imbalances in the degenerative brain microenvironment.

摘要

首次成功构建了负载天然抗氧化剂番茄红素(LYC)的重组人 H 铁蛋白纳米笼(rHuHF-LYC),旨在增加 LYC 在大脑中的含量,并探索这种纳米颗粒对神经退行性变的调节机制。在此,通过 D-半乳糖诱导的神经退行性变模型,基于行为分析、组织学观察、免疫染色分析、傅里叶变换红外显微镜和 Western blot 分析,研究了 rHuHF-LYC 的调节作用。rHuHF-LYC 可改善小鼠的行为,且呈剂量依赖性。此外,rHuHF-LYC 可以减轻神经元损伤,维持尼氏体数量,增加不饱和脂肪水平,抑制神经胶质细胞的激活,并防止神经毒性蛋白在小鼠海马中的过度积累。更重要的是,突触可塑性被激活,rHuHF-LYC 具有良好的生物相容性和生物安全性。本研究证明了直接使用天然抗氧化纳米药物治疗神经退行性变的有效性,为进一步改善退行性脑微环境的失衡提供了一种有前景的治疗选择。

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