Lukkarainen J, Kauppinen R A, Koistinaho J, Alhonen L M, Jänne J
NMR Research Group, A.I. Virtanen Institute, Kuopio, Finland.
Eur J Neurosci. 1995 Sep 1;7(9):1840-9. doi: 10.1111/j.1460-9568.1995.tb00704.x.
Cerebral ischaemia causes activation of ornithine decarboxylase followed by accumulation of putrescine, and these biochemical phenomena have been thought to contribute to the development of neuronal damage. We have used a transgenic mouse line overexpressing the human ornithine decarboxylase gene in their neurons with constitutively high putrescine to study the possible role of putrescine in development of neuronal damage in forebrain ischaemia. An incomplete forebrain ischaemia model was developed in which common carotid arteries were bilaterally occluded and reduction of blood pressure caused by orthostatic reaction was used as a way of decreasing cerebral circulation. Cerebral high-energy metabolites, intracellular pH and lactate were monitored by means of 31P and 1H nuclear magnetic resonance spectroscopy respectively. Incomplete ischaemia for 15 min resulted in severe energy failure, as indicated by an increase in the inorganic phosphate/phosphocreatine ratio, intracellular acidification from a pH of approximately 7.1 to approximately 6.5 and an increase in lactate concentration from < 1 to approximately 10 mmol/kg in both syngenic and transgenic mice. Following deocclusion, recovery of energy metabolites intracellular pH and lactate were identical in both animal groups. Ornithine decarboxylase activity rose 9- and 3-fold in syngenic and transgenic mice respectively 6 h after ischaemia, which was approximately 50-fold greater than the basal level in syngenic mice. In situ hybridization experiments revealed induction of transcription factors c-Fos and zif-268 in the hippocampus, throughout the cerebral cortex and striatum 1-3 h after ischaemia. Messenger RNA of heat shock protein 70 was induced in dentate gyrus and CA3 and CA4 subfields of the hippocampus 1 h after ischaemia.(ABSTRACT TRUNCATED AT 250 WORDS)
脑缺血会导致鸟氨酸脱羧酶激活，随后腐胺积聚，人们认为这些生化现象会促使神经元损伤的发展。我们使用了一种转基因小鼠品系，其神经元中过表达人类鸟氨酸脱羧酶基因，腐胺水平持续较高，以研究腐胺在前脑缺血性神经元损伤发展中的可能作用。构建了一种不完全性前脑缺血模型，通过双侧阻断颈总动脉，并利用直立反应导致的血压降低作为减少脑循环的一种方式。分别通过31P和1H核磁共振波谱法监测脑内高能代谢物、细胞内pH值和乳酸水平。15分钟的不完全缺血导致严重的能量衰竭，同基因和转基因小鼠的无机磷酸盐/磷酸肌酸比值升高、细胞内pH值从约7.1酸化至约6.5、乳酸浓度从<1 mmol/kg增至约10 mmol/kg均表明了这一点。解除阻断后，两个动物组的能量代谢物、细胞内pH值和乳酸的恢复情况相同。缺血6小时后，同基因和转基因小鼠的鸟氨酸脱羧酶活性分别升高了9倍和3倍，这比同基因小鼠的基础水平大约高50倍。原位杂交实验显示，缺血1 - 3小时后，海马体、整个大脑皮层和纹状体中诱导转录因子c-Fos和zif-268。缺血1小时后，海马齿状回以及海马体CA3和CA4亚区诱导热休克蛋白70的信使核糖核酸。（摘要截短于250字）
