Department of Neurosurgery, Juntendo University School of Medicine, Tokyo, Japan.
J Cereb Blood Flow Metab. 2011 Aug;31(8):1696-705. doi: 10.1038/jcbfm.2011.51. Epub 2011 Apr 13.
Glucagon-like peptide-1 (GLP-1) is an incretin hormone known to stimulate glucose-dependent insulin secretion. The GLP-1 receptor agonist, exendin-4, has similar properties to GLP-1 and is currently in clinical use for type 2 diabetes mellitus. As GLP-1 and exendin-4 confer cardioprotection after myocardial infarction, this study was designed to assess the neuroprotective effects of exendin-4 against cerebral ischemia-reperfusion injury. Mice received a transvenous injection of exendin-4, after a 60-minute focal cerebral ischemia. Exendin-4-treated vehicle and sham groups were evaluated for infarct volume, neurologic deficit score, various physiologic parameters, and immunohistochemical analyses at several time points after ischemia. Exendin-4 treatment significantly reduced infarct volume and improved functional deficit. It also significantly suppressed oxidative stress, inflammatory response, and cell death after reperfusion. Furthermore, intracellular cyclic AMP (cAMP) levels were slightly higher in the exendin-4 group than in the vehicle group. No serial changes were noted in insulin and glucose levels in both groups. This study suggested that exendin-4 provides neuroprotection against ischemic injury and that this action is probably mediated through increased intracellular cAMP levels. Exendin-4 is potentially useful in the treatment of acute ischemic stroke.
胰高血糖素样肽-1（GLP-1）是一种肠促胰岛素激素，已知可刺激葡萄糖依赖性胰岛素分泌。GLP-1 受体激动剂，exendin-4，具有与 GLP-1 相似的特性，目前用于 2 型糖尿病。由于 GLP-1 和 exendin-4 在心肌梗死后具有心脏保护作用，因此本研究旨在评估 exendin-4 对脑缺血再灌注损伤的神经保护作用。在 60 分钟局灶性脑缺血后，小鼠接受了 exendin-4 的静脉内注射。在缺血后几个时间点，对接受 exendin-4 治疗的载体和假手术组进行了梗死体积、神经功能缺损评分、各种生理参数和免疫组织化学分析。exendin-4 治疗显著减少了梗死体积并改善了功能缺损。它还显著抑制了再灌注后的氧化应激、炎症反应和细胞死亡。此外，exendin-4 组的细胞内环磷酸腺苷（cAMP）水平略高于载体组。两组的胰岛素和血糖水平均未出现连续变化。本研究表明，exendin-4 可提供针对缺血性损伤的神经保护作用，这种作用可能是通过增加细胞内 cAMP 水平介导的。exendin-4 在急性缺血性中风的治疗中可能有用。
