Edde L, Zhou X, Eaton J W, Sherman M P
Department of Pediatrics, Baylor College of Medicine, Houston, Texas 77030, USA.
Biochem Biophys Res Commun. 1998 Feb 24;243(3):683-7. doi: 10.1006/bbrc.1998.8163.
Intravenous fructose-1,6-diphosphate (FDP) is reported to reverse shock and improves survival in animals given systemic lipopolysaccharide (LPS), although the mechanism is incompletely understood. Since endotoxin-related shock is associated with increased nitric oxide (NO) production, LPS-stimulated macrophages were treated with FDP, and the NO metabolite, nitrite, was measured 24 h later. Treatment of LPS-stimulated macrophages with 1, 5, or 10 mM FDP caused a dose-dependent reduction in mRNA expression for inducible NO synthase by Northern analysis and decreased the micromolar concentrations of nitrite produced by 17, 42, and 68%, respectively. Neither fructose nor sodium phosphate had these effects in LPS-exposed macrophages. Electrophoretic mobility shift assays revealed that FDP did not inhibit LPS-mediated activation of nuclear factor kappa B. Viability analysis showed that the FDP effect was not caused by cytotoxicity. Overall, these results suggest that fructose-1,6-diphosphate, a glycolytic intermediate with potential clinical use, may mitigate the adverse effects of LPS by regulating the generation of NO.
据报道，静脉注射1,6 -二磷酸果糖（FDP）可逆转休克，并提高给予全身性脂多糖（LPS）的动物的存活率，尽管其机制尚不完全清楚。由于内毒素相关休克与一氧化氮（NO）产生增加有关，因此用FDP处理LPS刺激的巨噬细胞，并在24小时后测量NO代谢产物亚硝酸盐。用1、5或10 mM FDP处理LPS刺激的巨噬细胞，通过Northern分析导致诱导型NO合酶的mRNA表达呈剂量依赖性降低，并且使产生的亚硝酸盐微摩尔浓度分别降低了17%、42%和68%。果糖和磷酸钠在暴露于LPS的巨噬细胞中均无这些作用。电泳迁移率变动分析显示，FDP不抑制LPS介导的核因子κB的激活。活力分析表明，FDP的作用不是由细胞毒性引起的。总体而言，这些结果表明，1,6 -二磷酸果糖作为一种具有潜在临床用途的糖酵解中间产物，可能通过调节NO的生成来减轻LPS的不良反应。
