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短暂性脑缺血后大鼠脑内的单核苷酸代谢

Mononucleotide metabolism in the rat brain after transient ischemia.

作者信息

Onodera H, Iijima K, Kogure K

出版信息

J Neurochem. 1986 Jun;46(6):1704-10. doi: 10.1111/j.1471-4159.1986.tb08487.x.

DOI:10.1111/j.1471-4159.1986.tb08487.x
PMID:3701329
Abstract

Nucleotide metabolism was studied in rats during and following the induction of 10 min of forebrain ischemia (four-vessel occlusion model). Purine and pyrimidine nucleotides, nucleotides, and bases in forebrain extracts were quantitated by HPLC with an ultraviolet detector. Ischemia resulted in a severe reduction in the concentration of nucleoside triphosphates (ATP, GTP, UTP, and CTP) and an increase in the concentration of AMP, IMP, adenosine, inosine, hypoxanthine, and guanosine. During the recovery period, both the phosphocreatine level and adenylate energy charge were rapidly and completely restored to the normal range. ATP was only 78% of the control value at 180 min after ischemic reperfusion. Levels of nucleosides and bases were elevated during ischemia but decreased to values close to those of control animals following recirculation. Both the decrease in the adenine nucleotide pool and the incomplete ATP recovery were caused by insufficient reutilization of hypoxanthine via the purine salvage system. The content of cyclic AMP, which transiently accumulated during the early recirculation period, returned to the control level, paralleling the decrease of adenosine concentration, which suggested that adenylate cyclase activity during reperfusion is modulated by adenosine A2 receptors. The recovery of CTP was slow but greater than that of ATP, GTP, and UTP. The GTP/GDP ratio was higher than that of the control animals following recirculation.

摘要

在大鼠前脑缺血诱导10分钟期间及之后(四血管闭塞模型),对核苷酸代谢进行了研究。采用带紫外检测器的高效液相色谱法对前脑提取物中的嘌呤和嘧啶核苷酸、核苷酸及碱基进行定量分析。缺血导致三磷酸核苷(ATP、GTP、UTP和CTP)浓度严重降低,同时AMP、IMP、腺苷、肌苷、次黄嘌呤和鸟苷浓度升高。在恢复期间,磷酸肌酸水平和腺苷酸能荷迅速且完全恢复至正常范围。缺血再灌注180分钟时,ATP仅为对照值的78%。核苷和碱基水平在缺血期间升高,但再循环后降至接近对照动物的值。腺嘌呤核苷酸池的减少和ATP恢复不完全均是由于次黄嘌呤通过嘌呤补救系统再利用不足所致。早期再循环期间短暂积累的环磷酸腺苷含量恢复至对照水平,这与腺苷浓度的降低平行,提示再灌注期间腺苷酸环化酶活性受腺苷A2受体调节。CTP的恢复缓慢,但高于ATP、GTP和UTP。再循环后,GTP/GDP比值高于对照动物。

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