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体内烟酰胺腺嘌呤二核苷酸(NADH)荧光:戊巴比妥、吲哚美辛和水杨酸盐诱导的脑氧化代谢及灌注变化

NADH fluorescence in vivo: changes in cerebral oxidative metabolism and perfusion induced by pentobarbital, indomethacin, and salicylate.

作者信息

Nowicki J P, Jourdain D, MacKenzie E T

出版信息

J Cereb Blood Flow Metab. 1987 Jun;7(3):280-8. doi: 10.1038/jcbfm.1987.64.

DOI:10.1038/jcbfm.1987.64
PMID:3584263
Abstract

The effects of two prostaglandin synthesis inhibitors on brain oxidative metabolism and cerebral blood volume were studied by the nicotinamide adenine dinucleotide (reduced) (NADH) fluorescence technique in rats. Indomethacin (5, 10, and 15 mg/kg) and sodium salicylate (50, 100, and 300 mg/kg) were administered intravenously to groups of rats anesthetized with either nitrous oxide or pentobarbital (40 mg/kg, i.p.). The effects of pentobarbital alone were also examined: pentobarbital induced a progressive reduction in blood volume 4 min following intraperitoneal administration. A reduced NADH fluorescence (oxidation) was noted approximately 9 min after pentobarbital treatment. In N2O-anesthetized rats, the effects of salicylate were dose-dependent. Low doses (50 and 100 mg/kg) decreased both blood volume and NADH fluorescence; in contrast, salicylate at 300 mg/kg increased blood volume and NADH fluorescence. Following pentobarbital, the effects of salicylate (50 and 100 mg/kg) were reversed: increases in both blood volume and NADH fluorescence were seen. In the absence of pentobarbital, it would appear that salicylate induces a cerebral vasoconstriction, an effect that may be obscured by a central stimulation provoked by this drug. Under N2O anesthesia, indomethacin, in a dose-related manner, induced a decrease in blood volume that was accompanied by a dose-related increase in NADH fluorescence (reduction). The changes induced by the highest dose of indomethacin (15 mg/kg) were essentially abolished by pentobarbital. These results support those studies in which indomethacin-induced cerebral vasoconstriction could be abolished by barbiturates. Furthermore, our experiments demonstrate, following indomethacin infusion, a decrease in brain oxidative metabolism.(ABSTRACT TRUNCATED AT 250 WORDS)

摘要

采用烟酰胺腺嘌呤二核苷酸(还原型)(NADH)荧光技术,在大鼠中研究了两种前列腺素合成抑制剂对脑氧化代谢和脑血容量的影响。将吲哚美辛(5、10和15mg/kg)和水杨酸钠(50、100和300mg/kg)静脉注射给用氧化亚氮或戊巴比妥(40mg/kg,腹腔注射)麻醉的大鼠组。还研究了单独使用戊巴比妥的效果:腹腔注射戊巴比妥4分钟后,血容量逐渐减少。戊巴比妥治疗后约9分钟,观察到NADH荧光降低(氧化)。在氧化亚氮麻醉的大鼠中,水杨酸盐的作用呈剂量依赖性。低剂量(50和100mg/kg)可降低血容量和NADH荧光;相反,300mg/kg的水杨酸盐可增加血容量和NADH荧光。戊巴比妥给药后,水杨酸盐(50和100mg/kg)的作用发生逆转:血容量和NADH荧光均增加。在没有戊巴比妥的情况下,水杨酸盐似乎会引起脑血管收缩,这种作用可能会被该药物引起的中枢刺激所掩盖。在氧化亚氮麻醉下,吲哚美辛以剂量相关的方式引起血容量减少,并伴有NADH荧光(降低)的剂量相关增加。吲哚美辛最高剂量(15mg/kg)引起的变化基本上被戊巴比妥消除。这些结果支持了那些吲哚美辛诱导的脑血管收缩可被巴比妥类药物消除的研究。此外,我们的实验表明,输注吲哚美辛后,脑氧化代谢降低。(摘要截断于250字)

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