Exendin-4, a glucagon-like peptide-1 receptor agonist, provides neuroprotection in mice transient focal cerebral ischemia.
Exendin-4, a glucagon-like peptide-1 receptor agonist, provides neuroprotection in mice transient focal cerebral ischemia.
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DOI：
10.1038/jcbfm.2011.51
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发表时间：
2011-08
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影响因子：
--
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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相似的性质，目前临床用于治疗2型糖尿病。由于GLP-1和exendin-4在心肌梗死后赋予心脏保护作用，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。小鼠在60分钟的局灶性脑缺血后接受exendin-4的经静脉注射。在缺血后的几个时间点，评价Exendin-4处理的载体和假手术组的梗死体积、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治疗显著减少梗死体积并改善功能缺陷。它还显著抑制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AMP（cAMP）水平略高于溶剂组。两组的胰岛素和葡萄糖水平均未发生连续变化。这项研究表明，exendin-4提供了对缺血性损伤的神经保护，这种作用可能是通过增加细胞内cAMP水平介导的。Exendin-4在急性缺血性卒中的治疗中具有潜在的用途。
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.
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影响因子：
9.9
作者：
Bruno, A;Levine, SR;Fineberg, SE
通讯作者：
Fineberg, SE
影响因子：
2.9
作者：
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影响因子：
3.1
作者：
Kastin, AJ;Akerstrom, V;Pan, WH
通讯作者：
Pan, WH
DOI：
10.1124/jpet.102.037481
发表时间：
2002-09-01
影响因子：
3.5
作者：
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通讯作者：
Greig, NH
影响因子：
6.3
作者：
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通讯作者：
Urabe, Takao