Neuroprotective effects of N-stearoyltyrosine on transient global cerebral ischemia in gerbils
Neuroprotective effects of N-stearoyltyrosine on transient global cerebral ischemia in gerbils
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N-硬脂酰酪氨酸对沙鼠短暂性全脑缺血的神经保护作用
DOI：
10.1016/j.brainres.2009.06.070
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发表时间：
2009-09-01
期刊：
影响因子：
2.9
通讯作者：
Lu, Yang
中科院分区：
文献类型：
--
作者：
Zhang, Yan-Bin;Kan, Meng-Yuan;Lu, Yang
本研究首次观察了花生四烯酸（anandamide，AEA）类似物N-硬脂酰酪氨酸（N-stearoyltyrosine，NsTyr）对沙土鼠短暂性全脑缺血再灌注损伤的神经保护作用。采用行为学、被动回避实验、Morris水迷宫和组织病理学方法观察大鼠海马CA 1区锥体细胞的损伤情况。此外，使用末端脱氧核苷酸转移酶介导的UTP缺口末端标记（TUNEL）方法检测缺血诱导的细胞凋亡。此外，为了了解NsTyr的神经保护作用的机制，我们检查了抗氧化酶，如过氧化氢酶（CAT），超氧化物歧化酶（SOD），谷胱甘肽过氧化物酶（GSH-PX），和非酶清除剂谷胱甘肽（GSH），并测定了海马中丙二醛（MDA）的水平。NsTyr可减轻缺血再灌注损伤大鼠行为学和组织病理学的损害，降低MDA含量，显著提高抗氧化剂GSH和GSH-PX的活性，显著提高SOD和CAT的活性，提示NsTyr对全脑缺血再灌注损伤具有神经保护作用，其作用机制可能与抑制DNA断裂有关。抑制自由基的产生，提高抗氧化能力。(C)2009 Elsevier B. V.保留所有权利。
N-stearoyltyrosine (NsTyr), a synthesized anandamide (AEA) analogue, was evaluated for the first time in the present study for the neuroprotective effect in gerbils subjected to transient global cerebral ischemia reperfusion (IR). The extent of ischemia injury was assessed behaviorally by measuring neurological functions, passive avoidance test and Morris water maze; and histopathologically by evaluating hippocampal CA1 pyramidal damage. in addition, ischemia-induced apoptosis was examined using the terminal deoxynucleotidyl transferase-mediated UTP nick end labeling (TUNEL) method. Furthermore, in order to understand the mechanism of NsTyr's neuroprotective effect, we examined antioxidative enzymes, such as catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX), and non-enzymatic scavenger glutathione (GSH) and measured the levels of malondialdehyde (MDA) in hippocampus. The administration of NsTyr led to attenuation of ischemia-induced neural deficits both behaviorally and histopathologically, reduced the level of MDA, significantly increased the activity of antioxidants GSH and GSH-PX, and obviously elevated the activities of SOD and CAT. Our results suggest that NsTyr shows neuroprotective effect on global cerebral IR injury and its neuroprotective effects may be attributed to restraining DNA fragmentation, suppressing the production of free radicals and elevating antioxidant capacity. (C) 2009 Elsevier B.V. All rights reserved.