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内脂素-1 通过抑制小胶质细胞和半胱天冬酶-3 的激活改善短暂性全脑缺血/再灌注后空间记忆损伤。

Nesfatin-1 Improve Spatial Memory Impairment Following Transient Global Cerebral Ischemia/Reperfusion via Inhibiting Microglial and Caspase-3 Activation.

机构信息

Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.

Rayan Center for Neuroscience and Behavior, Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Iran.

出版信息

J Mol Neurosci. 2018 Jul;65(3):377-384. doi: 10.1007/s12031-018-1105-3. Epub 2018 Jun 28.

Abstract

Nesfatin-1, a recently discovered peptide, is involved in important functions such as food intake regulation and energy homeostasis. Previous studies have demonstrated that it has protective effects following myocardial injury and also protects dopaminergic cells against neurotoxicity with the anti-inflammatory and anti-apoptotic mechanisms. In this study, we aimed to assay the neuroprotective effects of Nesfatin-1 after brain ischemia/reperfusion. Twenty-eight male Wistar rats were randomly selected and allocated in the form of four groups (sham, Nesfatin-1, ischemia, ischemia+Nesfatin-1). Ischemia was created by obstruction couple common carotid arteries in 20-min period. Saline as a vehicle and Nesfatin-1 (20 μg/kg, intraperitoneally) were injected at the time of reperfusion. Spatial memory performances were evaluated by the Morris water maze. The level of protein expression was determined by immunohistochemical and immunofluorescence staining. Nesfatin-1 significantly reduced caspase-3 (P < 0.01) and microglial activation (P < 0.01) and improved spatial memory impairments (P < 0.05) induced by brain ischemia. Nesfatin-1 has significant neuroprotective effects and can be introduced as a therapeutic agent against cerebral ischemia-induced injuries.

摘要

内脂素-1 是一种最近发现的肽,参与了食物摄入调节和能量平衡等重要功能。先前的研究表明,它对心肌损伤具有保护作用,还通过抗炎和抗细胞凋亡机制保护多巴胺能细胞免受神经毒性。在这项研究中,我们旨在检测内脂素-1 在脑缺血/再灌注后的神经保护作用。28 只雄性 Wistar 大鼠被随机选择并分为四组(假手术、内脂素-1、缺血、缺血+内脂素-1)。通过阻塞双侧颈总动脉 20 分钟来制造缺血。再灌注时注射生理盐水作为载体和内脂素-1(20μg/kg,腹腔内)。通过 Morris 水迷宫评估空间记忆表现。通过免疫组织化学和免疫荧光染色测定蛋白质表达水平。内脂素-1 显著降低了缺血诱导的 caspase-3(P<0.01)和小胶质细胞激活(P<0.01),并改善了空间记忆障碍(P<0.05)。内脂素-1 具有显著的神经保护作用,可以作为治疗脑缺血引起损伤的药物。

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