Liu Peng, Zou Dan, Yi Long, Chen Mingliang, Gao Yanxiang, Zhou Rui, Zhang Qianyong, Zhou Yong, Zhu Jundong, Chen Ka, Mi Mantian
Research Center for Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University, Chongqing Key Laboratory of Nutrition and Food Safety, Chongqing Medical Nutrition Research Center, Chongqing, PR China.
Restor Neurol Neurosci. 2015;33(2):143-57. doi: 10.3233/RNN-140446.
Acute hypobaric hypoxia (HH) causes persistent cognitive impairment, affecting memory function specifically. Mitochondrial dysfunction and synaptic morphological change were the prominent pathological features of HH exposure on brain. Quercetin, a flavonoid found in fruits, vegetables, leaves and grains, is reported to prevent ischemia induced by neuronal injury. This study investigated the efficacy of quercetin to ameliorate HH-induced memory deficit.
Rats were exposed to HH equivalent to 5000 m for 7 days in a decompression chamber and received quercetin daily (50, 75 or 100 mg/kg·bw) via gavage during the period of exposure. Cognitive performance was assessed by the Morris water maze test. In vitro, the effect of quercetin was tested in hippocampus tissue.
Quercetin, especially at 100 mg/kg·bw, significantly reduced HH-induced memory decline. Meanwhile, HH-induced hippocampus mitochondrial and synaptic lesions were ameliorated by quercetin. Furthermore, quercetin regulated the expression of sirtuin 1(Sirt1), PGC-1α, and the proteins related with mitochondrial biogenesis and dynamics. Moreover, quercetin increased expression of fibronectin type III domain-containing protein 5 (FNDC5) and brain-derived neurotrophic factor (BDNF), showing the PGC-1α/FNDC5/BNDF pathways might be involved in neuronal adaptation.
The results suggest quercetin has prophylactic potential for amelioration of HH-induced memory impairment, which is associated with the mitochondrial and neuronal adaptation in hippocampus.
急性低压缺氧会导致持续的认知障碍，尤其会影响记忆功能。线粒体功能障碍和突触形态变化是低压缺氧暴露于大脑后的突出病理特征。槲皮素是一种存在于水果、蔬菜、叶子和谷物中的类黄酮，据报道可预防神经元损伤引起的缺血。本研究调查了槲皮素改善低压缺氧诱导的记忆缺陷的功效。
将大鼠置于减压舱中暴露于相当于海拔5000米的低压缺氧环境7天，并在暴露期间每天通过灌胃给予槲皮素（50、75或100毫克/千克体重）。通过莫里斯水迷宫试验评估认知能力。在体外，在海马组织中测试槲皮素的作用。
槲皮素，尤其是100毫克/千克体重时，显著降低了低压缺氧诱导的记忆衰退。同时，槲皮素改善了低压缺氧诱导的海马线粒体和突触损伤。此外，槲皮素调节了沉默调节蛋白1（Sirt1）、过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）以及与线粒体生物发生和动力学相关的蛋白质的表达。而且，槲皮素增加了含III型纤连蛋白结构域蛋白5（FNDC5）和脑源性神经营养因子（BDNF）的表达，表明PGC-1α/FNDC5/BDNF途径可能参与神经元适应。
结果表明槲皮素具有预防低压缺氧诱导的记忆损伤的潜力，这与海马体中的线粒体和神经元适应有关。
