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激光诱导兔视网膜损伤后的脂氧合酶代谢

Lipoxygenase metabolism following laser induced retinal injury in rabbits.

作者信息

Naveh N, Weissman C, Marshall J

机构信息

Sackler Faculty of Medicine, The Sheba Medical Center, Tel-Aviv University, The Goldschleger Eye Research Institute, Tel Hashomer, Israel.

出版信息

Curr Eye Res. 2000 Jul;21(1):554-9.

Abstract

PURPOSE

  1. to investigate whether leukotriene B(4) (LTB(4)) is a factor in the inflammatory reaction following chorioretinal laser injury in rabbits; 2) to study its relationship with the cyclooxygenase (COX) metabolic pathway; 3) to study the influence of Nordihydroguaiaretic acid (NDGA), an inhibitor; of the lipoxygenase (LOX) cascade, on both COX and LOX metabolism.

METHODS

Prostaglandin E(2) (PGE(2)) and LTB(4) synthesis by incubated samples of chorioretina obtained from rabbits' eyes exposed to Neodymium:Yag laser along with these eicosanoids accumulation in the vitreous were measured over one week follow-up period. The effect of NDGA pre-treatment on the COX and the LOX pathways in the laser-injured chorioretina was also assessed. PGE(2) and LTB(4) levels in the vitreous and in the chorioretina incubation medium were quantified using the radioimmunoassay technique with the appropriate antibodies.

RESULTS

LTB(4) in vitro production by rabbits' chorioretina subjected to ND; YAG laser was significantly elevated compared to control, peaking on day 7 to levels 2.45 fold greater than baseline (p < 0.01). PGE(2) formation, following a different pattern, was also enhanced and its maximal level (5.2 fold higher than control, p < 0.01) was achieved at the initial phase (day 1 post laser). Laser irradiation caused also an increase in the two eicosanoids accumulation in the vitreous, which was however not proportional to their production levels. NDGA treatment was associated with a sustained decrease in LTB(4) content in the vitreous, but had no effect on PGE(2) vitreal levels.

CONCLUSIONS

Laser irradiation of the rabbits' retina induces an alteration in the LOX metabolic pathway, which is dissociated from the influence on the COX cascade, pointing for the first time to a possible role played by LTB( 4) as a mediator in the chorioretinal inflammatory reaction, with no connection to the role played by PGE(2). NDGA selectively inhibited LOX activity without affecting COX activity.

摘要

目的

1)研究白三烯B4(LTB4)是否是兔脉络膜视网膜激光损伤后炎症反应的一个因素;2)研究其与环氧化酶(COX)代谢途径的关系;3)研究脂氧合酶(LOX)级联反应抑制剂去甲二氢愈创木酸(NDGA)对COX和LOX代谢的影响。

方法

在为期一周的随访期内,测量从接受钕钇铝石榴石激光照射的兔眼中获取的脉络膜视网膜孵育样本中前列腺素E2(PGE2)和LTB4的合成情况,以及这些类花生酸在玻璃体中的蓄积情况。还评估了NDGA预处理对激光损伤的脉络膜视网膜中COX和LOX途径的影响。使用放射性免疫分析技术和相应抗体对玻璃体和脉络膜视网膜孵育培养基中的PGE2和LTB4水平进行定量。

结果

与对照组相比,接受钕钇铝石榴石激光照射的兔脉络膜视网膜体外产生的LTB4显著升高,在第7天达到峰值,水平比基线高2.45倍(p<0.01)。PGE2的形成呈现不同模式,也有所增强,其最高水平(比对照组高5.2倍,p<0.01)在初始阶段(激光照射后第1天)达到。激光照射还导致玻璃体中这两种类花生酸的蓄积增加,然而这与它们的产生水平不成比例。NDGA治疗与玻璃体中LTB4含量持续降低有关,但对玻璃体中PGE2水平没有影响。

结论

兔视网膜激光照射诱导了LOX代谢途径的改变,这与对COX级联反应的影响无关,首次表明LTB4可能作为脉络膜视网膜炎症反应的介质发挥作用,与PGE2所起的作用无关。NDGA选择性抑制LOX活性而不影响COX活性。

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