Department of Pharmacy, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, PR China.
Brain Res. 2009 Sep 1;1287:146-56. doi: 10.1016/j.brainres.2009.06.070. Epub 2009 Jun 27.
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.
N-硬脂酰酪氨酸(NsTyr)是一种合成的大麻素(AEA)类似物,本研究首次评估了其在短暂全脑缺血再灌注(IR)后对沙土鼠的神经保护作用。通过测量神经功能、被动回避试验和 Morris 水迷宫,以及评估海马 CA1 锥体神经元损伤,从行为学和组织病理学两方面评估缺血损伤的程度。此外,采用末端脱氧核苷酸转移酶介导的 UTP 缺口末端标记法(TUNEL)检测缺血诱导的细胞凋亡。此外,为了了解 NsTyr 神经保护作用的机制,我们检测了抗氧化酶,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),并测量了海马丙二醛(MDA)的水平。NsTyr 的给药导致缺血诱导的神经功能缺损无论是在行为学上还是组织病理学上均减轻,降低 MDA 水平,显著增加抗氧化剂 GSH 和 GSH-PX 的活性,并明显提高 SOD 和 CAT 的活性。我们的结果表明,NsTyr 对全脑 IR 损伤具有神经保护作用,其神经保护作用可能归因于抑制 DNA 片段化、抑制自由基的产生和提高抗氧化能力。