Wang Pan, Sui Hai-Juan, Li Xiao-Jia, Bai Li-Na, Bi Jing, Lai Hong
Department of Anatomy, China Medical University, Shenyang; Department of Neurobiology and Key Laboratory of Neurodegenerative Diseases of Liaoning Province, Jinzhou Medical University; Department of Neurobiology, Jinzhou Medical University, Jinzhou, Liaoning Province, China.
Department of Neurobiology and Key Laboratory of Neurodegenerative Diseases of Liaoning Province; Department of Pharmacology, Jinzhou Medical University, Jinzhou, Liaoning Province, China.
Neural Regen Res. 2021 Apr;16(4):757-764. doi: 10.4103/1673-5374.295349.
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.
褪黑素可减轻心脏微血管缺血/再灌注损伤,但褪黑素是否也能改善脑微血管异常尚不清楚。通过每隔一天进行一次六次脑室内注射β-淀粉样蛋白1-42建立阿尔茨海默病大鼠模型。连续13天腹腔注射褪黑素(30mg/kg),第一剂在首次注射β-淀粉样蛋白1-42前24小时给予。褪黑素改善了莫里斯水迷宫试验中的学习和记忆障碍,改善了大脑皮层和海马体中微血管的形态,增加了微血管密度,减轻了脑神经元的病理损伤,并降低了血管内皮生长因子以及血管内皮生长因子受体1和2的表达。这些发现表明,褪黑素可通过降低血管内皮生长因子及其受体的表达来改善大脑皮层和海马体中的微血管异常,从而改善阿尔茨海默病患者的认知功能。本研究于2018年12月6日获得中国锦州医科大学动物护理和使用委员会批准(批准号:2019015)。