In vivo NMR study on the brain metabolism and biological active substabces under anesthesia and hypoxia

本文用~ 1C、~ 1 P和~ 1H核磁共振谱研究了缺氧和缺血时脑内葡萄糖代谢、能量状态和生物活性物质的变化<13><31>。雄性Wistar大鼠用氯胺酮（50- 75 mg/kg i. p.）机械通气：30%O_2，69.5%N_2和0.5%氟烷。[1-经<13>股静脉输注250 μ g/kg葡萄糖2次，每次间隔10 min。[1-[<13>1- 13 C]葡萄糖输注分别在92.7和96.7 ppm处给出[1- 13 C]葡萄糖的-和-端基异构体中的C1位置的明显信号<13>。谷氨酸（glu）中C2、C3和C4位置的信号也分别出现在55、27和34 ppm处。glu-C2和glu-C3信号的增强晚于glu-C4信号的增强。glu信号之间的时滞可能反映了TCA循环的周转率。在低氧实验中，吸入气体中O_2浓度降至6-7%（N_2浓度为93-94%）。在缺氧时，乳酸-^ C3信号<13>出现在 ...更多信息 21 ppm和增加，和-葡萄糖信号减弱，而-葡萄糖信号保持其强度。- 和-葡萄糖之间的信号强度变化的差异表明，-葡萄糖消耗更多的缺氧脑中的-葡萄糖。在低氧条件下，<31>30 min内磷酸肌酸（pcr）的ATP信号强度下降27%，而ATP信号无变化。在^1H谱中，乳酸-CH_3信号的增加也表明缺氧脑无氧糖酵解的增强。股静脉注射[1- 1C<13>]-葡萄糖（500 mg/kg）。葡萄糖注射后15 min，夹闭双侧颈总动脉造成脑缺血。在缺血脑中，-和-葡萄糖的信号迅速消失，乳酸- ^ C3的信号<13>变得突出。缺血时及缺血后均无谷氨酸信号。Pcr<31>和ATP的~（13）P谱均消失。因此，缺血脑不仅能荷降低，而且谷氨酸合成也降低。少

The glucose metabolism and the changes in energy state and biological active substances in the brain during hypoxia and ischemia were investigated by ^<13>C, ^<31>P and ^1H NMR spectroscopy. Male Wistar rats were anesthetized with ketamine (50-75mg/kg i.p.) and ventilated mechanically with a mixture of 30% O_2, 69.5% N_2 and 0.5% halothane. [1-^<13>C]glucose (250Mg/kg) was infused twice through femoral vein at 10 min interval. [1-^<13>C]Glucose infusion gave apparent signals of C1 position in - and - anomers of [1-^<13>C]glucose at 92.7 and 96.7 ppm, respectively. Signals of C2, C3 and C4 positions in glutamate (glu) also appeared at 55, 27 and 34 ppm, respectively. The intensity of glu-C2 and glu-C3 signals increased later than that of glu-C4. The time lag between the glu signals may reflect the turnover rate of the TCA cycle. In the hypoxic experiments, O_2 concentration in the inspiratory gas was reduced to 6-7% (93-94% N_2). During hypoxia, the signal of lactate-^<13>C3 appeared at … More 21 ppm and increased, and the -glucose signal diminished, whereas the -glucose signal kept its intensity. The difference in changes of the signal intensity between -and -glucose suggests that -glucose is consumed more than -glucose in the hypoxic brain. Under similar hypoxic condition, the ^<31>P signal intensity of creatine phosphate (pcr) decreased by 27% but the signal of ATP was unchanged in 30min. In the ^1H spectra, increase in the lactate-CH_3 signal also suggests the enhancement of anaerobic glycolisis in hypoxic brain.Mongolian gerbils were anesthetized with pentobarbital (35mg/kg, i.p.). A bolus of [1-^<13>C]-glucose (500mg/kg) was injected into femoral vein. Forbrain ischemia by bilateral common carotid occlusion was induced 15min after the glucose injection. In the ischemic brain, signals of both - and -glucose rapidly disappeared, and the signal of lactate- ^<13>C3 became prominent. The glutamate signals did not appeare during ischemia and even in post-ischemia. In the ^<31>P spectra, signals of both Pcr and ATP disappeared. Thereford, not only energy charge but also glutamate synthesis may be deperssed in the ischemic brain. Less