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[衰老对大鼠低血糖恢复后脑能量代谢的影响。药理学应用]

[The influence of aging on cerebral energy metabolism following post-hypoglycemic recovery in the rat. Pharmacologic application].

作者信息

Villa R F, Pastoris O

出版信息

J Pharmacol. 1986 Oct-Dec;17(4):623-36.

PMID:3560973
Abstract

Influence of aging on cerebral energetic metabolism was evaluated during and after severe hypoglycemia in rats respectively 20 (adults), 60 (matures) or 100 (senescents) week-old. Cerebral content of carbohydrates, amino-acids, ammonia, ATP, ADP, AMP, creatine phosphate and creatine was analysed after 20 min insulin induced hypoglycemia and after 20 min hypoglycemic recovery induced by glucose infusion. In the rats of different ages tested, effect of raubasine (0.85 mg X kg-1 i.p. and i.v.), almitrine (2.68 mg X kg-1 i.p. and i.v.) and association almitrine plus raubasine (at the same doses) on post-hypoglycemic recovery was tested. Aging does not affect the cerebral metabolic disorders occurring in severe hypoglycemia, but rather the metabolic changes during the post-hypoglycemic restitution. In fact there is lower restitution of the concentrations of cerebral cortical metabolites in older rats: the concentrations of many amino-acids and adenylate nucleotides remains largely abnormal. Compared with saline treated post-hypoglycemic rats, raubasine decreases by 15 to 20% cerebral glucose and pyruvate contents in "adults" and "matures" rats and by 10 to 15% glutamate content in rat of different ages tested. Almitrine decreases by 20% cerebral glucose concentration in "matures" and "senescent" rats. In this latter group, almitrine decreases lactate and ammonium contents and increases by 23% glutamine level. In rats of all ages that were submitted to 20 min insulin induced hypoglycemia followed by 20 min glucose induced post-hypoglycemic recovery, the association almitrine plus raubasine decreases by 20 to 30% cerebral glucose, pyruvate and lactate contents and decreases by 15% glutamate. In older brains the association almitrine plus raubasine decreases by 50% cerebral content in ammonium and concomitantly induces an equivalent increase in glutamine content. The effect of the combination almitrine plus raubasine is characterized by an increase in rate of metabolic recovery process in all ages tested.

摘要

分别在20周龄(成年)、60周龄(成熟)或100周龄(衰老)的大鼠严重低血糖期间及之后,评估衰老对大脑能量代谢的影响。在胰岛素诱导低血糖20分钟后以及葡萄糖输注诱导低血糖恢复20分钟后,分析大脑中碳水化合物、氨基酸、氨、三磷酸腺苷(ATP)、二磷酸腺苷(ADP)、一磷酸腺苷(AMP)、磷酸肌酸和肌酸的含量。在不同年龄的受试大鼠中,测试萝巴新(腹腔注射和静脉注射,剂量为0.85毫克/千克)、烯丙哌三嗪(腹腔注射和静脉注射,剂量为2.68毫克/千克)以及烯丙哌三嗪加萝巴新(相同剂量)对低血糖后恢复的影响。衰老并不影响严重低血糖时发生的大脑代谢紊乱,而是影响低血糖恢复期间的代谢变化。事实上,老年大鼠大脑皮质代谢物浓度的恢复较低:许多氨基酸和腺苷酸核苷酸的浓度在很大程度上仍异常。与生理盐水处理的低血糖后大鼠相比,萝巴新使“成年”和“成熟”大鼠的大脑葡萄糖和丙酮酸含量降低15%至20%,并使不同年龄受试大鼠的谷氨酸含量降低10%至15%。烯丙哌三嗪使“成熟”和“衰老”大鼠的大脑葡萄糖浓度降低20%。在这后一组中,烯丙哌三嗪降低乳酸和铵含量,并使谷氨酰胺水平升高23%。在所有年龄的大鼠中,先进行20分钟胰岛素诱导的低血糖,随后进行20分钟葡萄糖诱导的低血糖后恢复,烯丙哌三嗪加萝巴新使大脑葡萄糖、丙酮酸和乳酸含量降低20%至30%,并使谷氨酸含量降低15%。在老年大脑中,烯丙哌三嗪加萝巴新使大脑铵含量降低50%,并同时使谷氨酰胺含量等量增加。烯丙哌三嗪加萝巴新组合的作用特点是在所有受试年龄中代谢恢复过程的速率增加。

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