Ouyang Y B, He Q P, Zhang X H, Wang G X, Siesjö B K, Hu B R
Center for the Study of Neurological Disease, The Queen's Medical Center, Honolulu, Hawaii, USA.
J Cereb Blood Flow Metab. 2000 Nov;20(11):1550-6. doi: 10.1097/00004647-200011000-00004.
In the current study, the temporal and regional changes of the transcription factor cyclic adenosine monophosphate response element binding protein (CREB) were investigated in rat brains subjected to 30 minutes of hypoglycemic coma followed by varied periods of recovery using Western blot and confocal microscopy. The total amount of CREB was not altered in any area examined after coma. The level of the phosphorylated form of CREB decreased during coma but rebounded after recovery. In the relatively resistant areas, such as the inner layers of the neocortex and the inner and outer blades of the dentate gyms (DG), phospho-CREB increased greater than the control level after 30 minutes of recovery and continued to increase up to 3 hours of recovery. In contrast, little or no increase of phospho-CREB was observed during the recovery period in the outer layers of the neocortex and at the tip of the DG, that is, regions that are selectively vulnerable to hypoglycemic insults. The current findings suggest that a neuroprotective signaling pathway may be more activated in the resistant regions than in the vulnerable ones after hypoglycemic coma.
在当前研究中,使用蛋白质免疫印迹法和共聚焦显微镜,对经历30分钟低血糖昏迷并随后进行不同时长恢复的大鼠大脑中转录因子环磷酸腺苷反应元件结合蛋白(CREB)的时间和区域变化进行了研究。昏迷后,在所检查的任何区域中CREB的总量均未改变。CREB的磷酸化形式水平在昏迷期间下降,但恢复后反弹。在相对抗损伤的区域,如新皮质内层以及齿状回(DG)的内叶片和外叶片,恢复30分钟后磷酸化CREB增加至高于对照水平,并在恢复长达3小时的时间内持续增加。相比之下,在新皮质外层和DG尖端(即对低血糖损伤选择性敏感的区域)的恢复期间,未观察到磷酸化CREB有很少增加或没有增加。目前的研究结果表明,低血糖昏迷后,抗损伤区域可能比敏感区域更能激活神经保护信号通路。