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缺氧发育中大鼠脑内磷酸肌酸和三磷酸腺苷的调节

Phosphocreatine and ATP regulation in the hypoxic developing rat brain.

作者信息

Tsuji M, Allred E, Jensen F, Holtzman D

机构信息

Joint Program in Neonatology, Harvard Medical School, Boston, MA 02115, USA.

出版信息

Brain Res Dev Brain Res. 1995 Apr 18;85(2):192-200. doi: 10.1016/0165-3806(94)00213-j.

DOI:10.1016/0165-3806(94)00213-j
PMID:7600667
Abstract

Decreased brain ATP and phosphocreatine (PCr) concentrations and intracellular pH were compared in hypoxic 4-, 10-11, and 24-25-day-old rats. Surface coil 31P-nuclear magnetic resonance (NMR) spectra were acquired in vivo every minute before, during, and after 7 min of breathing 4% O2. At all ages PCr decreased rapidly. At the two younger ages, the nucleoside triphosphate signal was still 80-85% of pre-hypoxic values, indicating 20-30% decrease in ATP, when PCr was almost fully depleted. At 24-25 days, PCr initially decreased 40-50% with an ATP loss of about 30%. Then, PCr and ATP decreased simultaneously. The decrease in brain pH was greatest at 24-25 days. More electrocortical seizure activity during hypoxia was seen at 10-11 days than at other ages. Seizure activity was seen only when ATP was less than 20% depleted and was not associated with more rapid decreases in ATP or PCr. At all ages, loss of electrocortical activity occurred when ATP was about 30% depleted. Brain creatine kinase catalyzed flux, measured by the NMR saturation transfer experiment before the hypoxic period, was 4-fold higher at 24-25 days than at 4- or 10-11 days. In conclusion, the temporally coupled depletion of PCr and ATP during hypoxia, which is characteristic of the mature brain, is seen only after the maturational increase in brain CK activity.

摘要

对4日龄、10 - 11日龄和24 - 25日龄的缺氧大鼠的脑ATP和磷酸肌酸(PCr)浓度以及细胞内pH值进行了比较。在呼吸4%氧气7分钟之前、期间和之后,每分钟利用表面线圈进行体内31P - 核磁共振(NMR)光谱采集。在所有年龄段,PCr均迅速下降。在两个较年幼的年龄段,当PCr几乎完全耗尽时,核苷三磷酸信号仍为缺氧前值的80 - 85%,表明ATP下降了20 - 30%。在24 - 25日龄时,PCr最初下降40 - 50%,ATP损失约30%。然后,PCr和ATP同时下降。脑pH值的下降在24 - 25日龄时最为明显。在10 - 11日龄时,缺氧期间观察到的皮层电癫痫活动比其他年龄段更多。癫痫活动仅在ATP消耗少于20%时出现,且与ATP或PCr的更快下降无关。在所有年龄段,当ATP消耗约30%时,皮层电活动消失。通过缺氧期前的NMR饱和转移实验测量的脑肌酸激酶催化通量,在24 - 25日龄时比4日龄或10 - 11日龄时高4倍。总之,缺氧期间PCr和ATP的时间耦合性消耗是成熟脑的特征,这种情况仅在脑CK活性成熟增加之后才会出现。

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