Medical School of China Three Gorges University, Yichang 443002, PR China.
The First Renmin Hospital of Yichang City, Yichang 443002, PR China.
Eur J Pharmacol. 2018 Jan 5;818:167-173. doi: 10.1016/j.ejphar.2017.10.041. Epub 2017 Oct 23.
Clonidine, a classical α-2 adrenergic agonists, has been shown to antagonize brain damage caused by hypoxia, cerebral ischemia and excitotoxicity and reduce cerebral infarction volume in recent studies. We herein investigate the regulatory effect and possible underlying mechanism of clonidine on learning and memory in rats with cerebral ischemia. The cerebral ischemia rat model was established by right middle cerebral artery occlusion for 2h and reperfusion for 28 days. Drugs were administrated to the rats for consecutive 7 days intraperitoneally and once again on the day of surgery. The learning and memory in rats was assayed by Morris water maze. Moreover, protein expression levels of NMDAR2B (NR2B)/ phosphor - NR2B, ERK1/2/phosphor- ERK1/2, CREB/phosphor-CREB and NF-κB/phosphor-NF-κB in the cortex and hippocampus of the rats were assayed by western blotting. Our results demonstrated that clonidine treatment significantly abrogated the negative effect induced by cerebral ischemia on the learning and memory in the rats. In the Western blotting assay, clonidine treatment led to significant up-regulation of the expression level of NR2B and Phospho-NR2B in the hippocampus of the rats when compared with the cerebral ischemia group. Furthermore, clonidine also significantly decreased the protein expression levels of ERK1/2, Phospho-ERK1/2, CREB, Phospho-CREB and Phospho-NF-κB in the hippocampus of the rats when compared with the cerebral ischemia group. In conclusion, clonidine could improve the learning and memory ability of rats with cerebral ischemia, and NR2B, ERK1/2, CREB, NF-κB were involved in this effect.
可乐定，一种经典的 α-2 肾上腺素能激动剂，最近的研究表明，它可以拮抗缺氧、脑缺血和兴奋性毒性引起的脑损伤，并减少脑梗死体积。我们在此研究可乐定对脑缺血大鼠学习记忆的调节作用及可能的机制。通过右侧大脑中动脉闭塞 2 小时再灌注 28 天建立脑缺血大鼠模型。药物连续 7 天腹腔注射，手术当天再次给药。Morris 水迷宫检测大鼠学习记忆能力。Western blot 检测大鼠皮质和海马中 NMDAR2B（NR2B）/磷酸化 NR2B、ERK1/2/磷酸化 ERK1/2、CREB/磷酸化 CREB 和 NF-κB/磷酸化 NF-κB 的蛋白表达水平。结果表明，可乐定治疗显著减轻了脑缺血对大鼠学习记忆的负面影响。Western blot 检测结果显示，与脑缺血组相比，可乐定治疗可显著上调大鼠海马 NR2B 和磷酸化 NR2B 的表达水平。此外，与脑缺血组相比，可乐定还显著降低了大鼠海马中 ERK1/2、磷酸化 ERK1/2、CREB、磷酸化 CREB 和磷酸化 NF-κB 的蛋白表达水平。结论：可乐定可改善脑缺血大鼠的学习记忆能力，NR2B、ERK1/2、CREB、NF-κB 参与了这一作用。
