Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan.
Neurosci Lett. 2010 Oct 22;484(1):43-6. doi: 10.1016/j.neulet.2010.08.015. Epub 2010 Aug 13.
We previously reported the effect of a selective inducer of BiP (a BiP inducer X; BIX) after permanent middle cerebral artery occlusion (MCAO) in mice. However, in acute stroke, almost all drugs have been used clinically after the onset of events. We evaluated the effect of post-treatment of BIX after permanent MCAO in mice, and examined its neuroprotective properties in in vivo mechanism. BIX (intracerebroventricular injection at 20μg) administered either at 5min or 3h after occlusion reduced both infarct volume and brain swelling, but at 6h after occlusion there was no reduction. BIX protected against the decrease in a dose-dependent manner. Furthermore, BIX reduced the number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL)-positive cells induced by the ischemia in ischemic penumbra. These findings indicate that post-treatment with BIX after ischemia has neuroprotective effects against acute ischemic neuronal damage in mice even when given up to 3h after MCAO. BIX may therefore be a potential drug for stroke.
我们之前报道了一种选择性诱导 BiP（一种 BiP 诱导剂 X；BIX）的药物在小鼠永久性大脑中动脉闭塞（MCAO）后的作用。然而，在急性脑卒中中，几乎所有药物都是在发病后才开始临床应用的。我们评估了在小鼠永久性 MCAO 后给予 BIX 治疗的效果，并在体内机制中研究了其神经保护特性。BIX（在闭塞后 5 分钟或 3 小时通过脑室内注射给予 20μg）给药可降低梗死体积和脑水肿，但在闭塞后 6 小时则没有降低。BIX 以剂量依赖性方式保护神经元免受损伤。此外，BIX 还减少了由缺血诱导的缺血半影区中末端脱氧核苷酸转移酶介导的 dUTP 缺口末端标记（TUNEL）阳性细胞的数量。这些发现表明，即使在 MCAO 后 3 小时给予 BIX，缺血后给予 BIX 治疗也具有对抗急性缺血性神经元损伤的神经保护作用。因此，BIX 可能是一种用于治疗脑卒中的潜在药物。
