Benzi G, Pastoris O, Villa R F, Giuffrida A M
Biochem Pharmacol. 1985 May 1;34(9):1477-83. doi: 10.1016/0006-2952(85)90687-2.
In rats of different ages, acute severe hypoglycemia with isoelectric EEG induced extensive deterioration of the energy state and gross alteration of amino acid contents. During recovery of adult animals, tissue glucose concentration returned to normal, while the rate of glycogen synthesis was slow, both lactate and pyruvate concentrations increasing above normal. In the recovery period of "adult" rats, the ATP concentration increased but the adenine nucleotide pool remained reduced, even if the ADP and AMP concentrations were close to normal. Phosphocreatine was restored to normal concentrations with reciprocal changes in creatine content. In adult rats, during the recovery there was a rise in glutamate and glutamine concentrations, gamma-aminobutyrate concentration returning to normal value. Ammonia and aspartate decreased below normal, while alanine increased above normal. Aging does not affect the cerebral metabolic derangement occurring in severe hypoglycemia, but rather the metabolic changes that the brain tends to reverse during the posthypoglycemic restitution. In fact, there was lower restitution of the concentrations of cerebral cortical metabolites of "mature" and "senescent" rats in comparison with "adult" ones. Particularly, in older brains the concentrations of many amino acids and adenylate nucleotides remained largely abnormal. The effect of some agents on the posthypoglycemic recovery was tested: (a) dihydroergocristine; (b) eburnamonine; (c) raubasine; (d) almitrine; (e) piracetam. During the posthypoglycemic recovery, these different agents exhibited different interferences on glycolytic metabolites, amino acids and energy-rich phosphates. However, a more limited effect of the tested agents, which decrease with aging, was observed.
在不同年龄的大鼠中，伴有脑电图等电位的急性严重低血糖会导致能量状态广泛恶化以及氨基酸含量显著改变。在成年动物恢复过程中，组织葡萄糖浓度恢复正常，但糖原合成速率缓慢，乳酸和丙酮酸浓度均高于正常水平。在“成年”大鼠的恢复期，ATP浓度升高，但腺嘌呤核苷酸池仍减少，即便ADP和AMP浓度接近正常。磷酸肌酸恢复到正常浓度，同时肌酸含量发生相应变化。在成年大鼠恢复过程中，谷氨酸和谷氨酰胺浓度升高，γ-氨基丁酸浓度恢复到正常值。氨和天冬氨酸低于正常水平，而丙氨酸高于正常水平。衰老并不影响严重低血糖时发生的脑代谢紊乱，而是影响大脑在低血糖后恢复过程中倾向于逆转的代谢变化。事实上，与“成年”大鼠相比，“成熟”和“衰老”大鼠大脑皮质代谢物浓度的恢复程度较低。特别是，在老年大脑中，许多氨基酸和腺苷酸核苷酸的浓度在很大程度上仍异常。测试了某些药物对低血糖后恢复的影响：(a)双氢麦角克碱；(b)长春胺；(c)萝巴新；(d)烯丙哌三嗪；(e)吡拉西坦。在低血糖后恢复过程中，这些不同药物对糖酵解代谢物、氨基酸和高能磷酸盐表现出不同的干扰。然而，观察到所测试药物的作用较为有限，且随衰老而减弱。
