中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (4): 787-794.doi: 10.4103/1673-5374.295349

• 原著:退行性病与再生 • 上一篇    下一篇

褪黑素可改善阿尔茨海默病大脑皮质和海马中微血管的异常

  

  • 出版日期:2021-04-15 发布日期:2020-12-22
  • 基金资助:
    中国国家自然科学基金项目(81370462),辽宁省攀登支持计划,辽宁医科大学校长基金(20140107),辽宁省自然科学基金项目(20180551185)

Melatonin ameliorates microvessel abnormalities in the cerebral cortex and hippocampus in a rat model of Alzheimer’s disease

Pan Wang1, 2, 3, Hai-Juan Sui2, 4, Xiao-Jia Li2, 3, Li-Na Bai2, 3, Jing Bi2, 3, *, Hong Lai1, *   

  1. 1 Department of Anatomy, China Medical University, Shenyang, Liaoning Province, China;  2 Department of Neurobiology and Key Laboratory of Neurodegenerative Diseases of Liaoning Province, Jinzhou Medical University, Jinzhou, Liaoning Province, China;  3 Department of Neurobiology, Jinzhou Medical University, Jinzhou, Liaoning Province, China;  4 Department of Pharmacology, Jinzhou Medical University, Jinzhou, Liaoning Province, China
  • Online:2021-04-15 Published:2020-12-22
  • Contact: Hong Lai, PhD, hlai@cmu.edu.cn; Jing Bi, PhD, jing_b@jzmu.edu.cn.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, No. 81370462 (to JB), the Climbing Scholars Support Plan of Liaoning Province of China (to JB), and the Principal’s Fund of Liaoning Medical University of China, No. 20140107 (to PW), the Natural Science Foundation of Liaoning Province of China, No. 20180551185 (to PW).

摘要:

最近有研究显示褪黑素可改善心脏微血管缺血再灌注损伤,但尚不清楚其是否也可改善阿尔茨海默病大脑微血管的异常。(1)实验通过脑室注射可溶性Aβ1-42隔天一次,连续6次,建立阿尔茨海默病大鼠模型。于首次Aβ1-42给药前24h,腹腔注射30 mg/kg褪黑素,连续给药13d。结果发现,褪黑素可改善阿尔茨海默病模型大鼠的Morris水迷宫空间学习和记忆能力,改善大脑皮质和海马微血管形态,增加微血管密度,且减轻大脑神经元病理损伤,褪黑素也降低了大脑中血管内皮生长因子及其受体1和2的表达;(2)结果显示,褪黑素可通过调节血管内皮生长因子及其受体表达,改善大脑皮质和海马中微血管的异常,进而改善阿尔茨海默病的认知功能。实验于2018年12月6日经锦州医科大学动物伦理委员会批准,批准号2019015。

https://orcid.org/0000-0002-6085-824X (Hong Lai); 

https://orcid.org/0000-0001-8959-0999 (Jing Bi)

关键词: 中枢神经系统, 脑, 阿尔茨海默病, 模型, 大鼠, 体内, 蛋白, 因子, 通路

Abstract: Melatonin can attenuate cardiac microvascular ischemia/reperfusion injury, but it remains unclear whether melatonin can also ameliorate cerebral microvascular abnormalities. Rat models of Alzheimer’s disease were established by six intracerebroventricular injections of amyloid-beta 1–42, administered once every other day. Melatonin (30 mg/kg) was intraperitoneally administered for 13 successive days, with the first dose given 24 hours prior to the first administration of amyloid-beta 1–42. Melatonin ameliorated learning and memory impairments in the Morris water maze test, improved the morphology of microvessels in the cerebral cortex and hippocampus, increased microvessel density, alleviated pathological injuries of cerebral neurons, and decreased the expression of vascular endothelial growth factor and vascular endothelial growth factor receptors 1 and 2. These findings suggest that melatonin can improve microvessel abnormalities in the cerebral cortex and hippocampus by lowering the expression of vascular endothelial growth factor and its receptors, thereby improving the cognitive function of patients with Alzheimer’s disease. This study was approved by the Animal Care and Use Committee of Jinzhou Medical University, China (approval No. 2019015) on December 6, 2018.

Key words: Alzheimer’s disease, brain, central nervous system, factor, in vivo, model, pathways, protein, rat