果糖-1,6-二磷酸增强了地塞米松对小鼠缺血性和组胺性爪肿胀的氧自由基及一氧化氮依赖性抑制作用。

Fructose-1,6-diphosphate enhanced oxyradicals and nitric oxide-dependent suppressions by dexamethasone of ischemic and histamine paw edema of mice.

作者信息

Oyanagui Y

机构信息

2nd Pharmacology, Drug Development Laboratories of Fujisawa Pharmaceutical Co., Osaka, Japan.

出版信息

Life Sci. 1998;62(15):PL241-9. doi: 10.1016/s0024-3205(98)00073-3.

DOI:10.1016/s0024-3205(98)00073-3

PMID:9566781

Abstract

Dexamethasone (Dex, 0.1 mg/kg, s.c.) suppressions of ischemic paw edema in mice at 1, 3, 6, 8, 18 hr were; 2, 22, 12, 11, 7%. Dex suppression in fructose-1,6-diphosphate (FDP, 100 mg/kg, i.p.)-treated mice were; 5, 49, 51, 42, 33%. Suppressions by this dose of FDP alone were less than 10% during 0-18 hr. ED30 at 6 hr of Dex +/- FDP was: 80 versus 500 mg/kg in ischemic-, and 5 versus 30 mg/kg in histamine edema. Endogenous oxyradicals or NO and protein synthesis were essential for suppressions. FDP may not change glucocorticoid receptor (GR) conformation, but increase ATP-dependent GR recycling efflux from nucleus. FDP is possible to supply this ATP. Clinical trial of FDP with low dose of Dex seems advantageous.

摘要

地塞米松（Dex，0.1毫克/千克，皮下注射）在1、3、6、8、18小时对小鼠缺血性爪水肿的抑制率分别为2%、22%、12%、11%、7%。在经1,6 - 二磷酸果糖（FDP，100毫克/千克，腹腔注射）处理的小鼠中，地塞米松的抑制率分别为5%、49%、51%、42%、33%。单独使用该剂量的FDP在0至18小时内的抑制率小于10%。地塞米松±FDP在6小时时的半数有效剂量（ED30）为：在缺血性水肿中，分别为80毫克/千克和500毫克/千克；在组胺性水肿中，分别为5毫克/千克和30毫克/千克。内源性氧自由基或一氧化氮以及蛋白质合成对于抑制作用至关重要。FDP可能不会改变糖皮质激素受体（GR）的构象，但会增加ATP依赖的GR从细胞核的再循环外流。FDP有可能提供这种ATP。低剂量地塞米松与FDP的临床试验似乎具有优势。