Effect of glucose on recovery of energy metabolism following hypoxia-oligemia in mouse brain: dose-dependence and carbohydrate specificity.
Effect of glucose on recovery of energy metabolism following hypoxia-oligemia in mouse brain: dose-dependence and carbohydrate specificity.
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葡萄糖对小鼠脑缺氧低血症后能量代谢恢复的影响：剂量依赖性和碳水化合物特异性。
DOI：
10.1038/jcbfm.1983.75
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发表时间：
1983
期刊：
影响因子：
--
通讯作者：
McKee,AE
中科院分区：
文献类型：
--
作者：
Welsh,FA;Sims,RE;McKee,AE
颈动脉闭塞联合全身缺氧（10% O2）麻醉小鼠产生单侧脑缺氧-低血症。在颈动脉闭塞同侧的大脑皮层中，ATP水平在30分钟的损伤期间被耗尽，但在60分钟的恢复期间恢复到对照组的64%。葡萄糖预处理动物以剂量依赖的方式减少ATP的恢复。因此，当血糖水平超过12-13 mM（225 mg/dl）时，ATP的恢复受到严重损害。半乳糖和3- o -甲基葡萄糖都没有模仿葡萄糖的有害作用。然而，甘露糖预处理容易被大脑代谢，损害了ATP的恢复。因此，这种损伤似乎是脑代谢底物所特有的。当血糖水平远高于ATP恢复阈值时，同侧皮质乳酸的缺血性积累仅增加30%。因此，除非能量代谢的恢复对脑乳酸的小增量敏感，否则很难在乳酸性酸中毒增强的基础上解释葡萄糖诱导的能量衰竭。在缺氧和恢复期间，用[14C]碘安替比林测量同侧脑血流量（CBF），葡萄糖预处理的动物比盐水预处理的动物低。然而，在相同的组织样本中，在恢复15分钟时测量的CBF和ATP之间的相关性较差，无法证实ATP的再生在恢复早期受到流量限制。
Unilateral cerebral hypoxia–oligemia was produced in anesthetized mice using carotid artery occlusion combined with systemic hypoxia (10% O2). In the cerebral cortex ipsilateral to the carotid occlusion, ATP levels were depleted during a 30-min insult, but were restored to 64% of control during 60 min of recovery. Pretreatment of animals with glucose diminished the restoration of ATP in a dose-dependent manner. Thus, when blood glucose levels exceeded 12–13 mM(225 mg/dl), ATP recovery was greatly impaired. Neither galactose nor 3-O-methylglucose mimicked the detrimental effect of glucose. However, pretreatment with mannose, which is readily metabolized by brain, impaired restoration of ATP. The impairment, therefore, appears to be specific for substrates of cerebral metabolism. The ischemic accumulation of lactate in the ipsilateral cortex was augmented by only 30% at blood glucose levels well above the threshold for ATP recovery. Thus, unless recovery of energy metabolism is sensitive to small increments in brain lactate, it is difficult to explain the glucose-induced energy failure on the basis of enhanced lactic acidosis. Ipsilateral cerebral blood flow (CBF), measured with [14C]iodoantipyrine during hypoxia and recovery, was lower in glucose-pretreated than in saline-pretreated animals. However, the poor correlation between CBF and ATP, measured in the same tissue samples at 15 min recovery, failed to substantiate that regeneration of ATP was flow-limited early in recovery.