中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (1): 226-232.doi: 10.4103/1673-5374.344841

• 原著:退行性病与再生 • 上一篇    

乳铁蛋白修饰可提高小檗碱脂质体对阿尔茨海默病的神经保护作用

  

  • 出版日期:2023-01-15 发布日期:2022-06-17
  • 基金资助:

    深圳市三明医药健康项目(SZSM201612049);深圳市学科布局基础研究项目(JCYJ20170413161352000);广东省基础研究计划项目(2020A1515011427

Lactoferrin modification of berberine nanoliposomes enhances the neuroprotective effects in a mouse model of Alzheimer’s disease

Lin Wang1, #, Bi-Qiang Zhou2, #, Ying-Hong Li2, Qian-Qian Jiang1, Wei-Hong Cong3, Ke-Ji Chen3, *, Xiao-Min Wen4, *, Zheng-Zhi Wu1, *   

  1. 1The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen Institute of Geriatrics, Shenzhen, Guangdong Province, China; 2The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, Guangdong Province, China; 3China Academy of Chinese Medical Sciences, Xiyuan Hospital, Beijing, China; 4School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong Province, China
  • Online:2023-01-15 Published:2022-06-17
  • Contact: Ke-Ji Chen, kjchenvip@163.com; Xiao-Min Wen, PhD, wxm@smu.edu.cn; Zheng-Zhi Wu, PhD, szwzz001@email.szu.edu.cn.
  • Supported by:
    This study was financially supported by Shenzhen Sanming Project of Medicine and Health, No. SZSM201612049 (to KJC); the Shenzhen Municipal Basic Research Project for Discipline Layout of China, No. JCYJ20170413161352000 (to YHL); and Guangdong Basic Research Project, No. 2020A1515011427 (to ZZW).

摘要:

既往研究显示,小檗碱有拮抗Tau磷酸化、抑制乙酰胆碱酯酶活性和神经细胞凋亡、神经保护作用等抗阿尔茨海默病的作用,但其常规给药后存在生物利用度低和不良反应大的问题。实验采用具有低毒、高封装率、生物降解等优点的脂质体对小檗碱进行剂型改良,并以具有脑靶向功能的乳铁蛋白进行修饰,制备的乳铁蛋白修饰小檗碱纳米脂质体粒径分布均匀且包封率高。然后将这种脂质体用于治疗Aβ1-42侧脑室注射建立的阿尔茨海默病小鼠模型,结果显示,乳铁蛋白的修饰能提高小檗碱脂质体进入小鼠脑部的药物浓度,可抑制海马组织中乙酰胆碱酯酶活性、减轻大脑皮质中Tau蛋白过度磷酸化和神经细胞凋亡,并改善小鼠的行为能力。提示乳铁蛋白修饰可提高小檗碱纳米脂质体对阿尔茨海默病的神经保护作用。

https://orcid.org/0000-0002-8819-609X (Zheng-Zhi Wu)

关键词:

阿尔茨海默病, 小檗碱, 纳米脂质体, 乳铁蛋白, 脑靶向, 神经保护, Tau磷酸化, 乙酰胆碱酯酶, 细胞凋亡

Abstract: Previous studies have shown that berberine has neuroprotective effects against Alzheimer’s disease, including antagonizing tau phosphorylation, and inhibiting acetylcholinesterase activity and neural cell apoptosis. However, its low bioavailability and adverse reactions with conventional administration limit its clinical application. In this study, we prepared berberine nanoliposomes using liposomes characterized by low toxicity, high entrapment efficiency, and biodegradability, and modified them with lactoferrin. Lactoferrin-modified berberine nanoliposomes had uniform particle size and high entrapment efficiency. We used the lactoferrin-modified berberine nanoliposomes to treat a mouse model of Alzheimer’s disease established by injection of amyloid-beta 1–42 into the lateral ventricle. Lactoferrin-modified berberine nanoliposomes inhibited acetylcholinesterase activity and apoptosis in the hippocampus, reduced tau over-phosphorylation in the cerebral cortex, and improved mouse behavior. These findings suggest that modification with lactoferrin can enhance the neuroprotective effects of berberine nanoliposomes in Alzheimer’s disease.

Key words: acetylcholinesterase, Alzheimer’s disease, apoptosis, berberine, brain targeting, lactoferrin, nanoliposomes, neuroprotective effects, Tau phosphorylation