Increased thromboxane A2 and 5-HETE production following spinal cord ischemia in the rabbit

E. Shohami , T.P. Jacobs , J.M. Hallenbeck , G. Feuerstein ∗
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引用次数: 28

Abstract

Ischemia was induced for 25 min in the spinal cord of rabbits followed by a long term period of recirculation. At various time points of recirculation (5, 30 min, 4, 18 hr and 1 wk) slices were taken from the ischemic region and incubated for 45 min in Krebs-Ringer solution. The levels of the eicosanoids, PGE2, PGD2, PGF, TXB2, 6-keto-PGF and 5-HETE accumulated in the incubation medium were measured by radioimmunoassay.

TXB2 release was found to be increased at an early (5 min) and late (1 wk) period of reperfusion. A seven-fold increase in the release of 5-HETE was found 5 min after reperfusion that tended to stay elevated at 18 hr and 1 week of recirculation. PGI2 synthetase activity decreased by 40% at 30 min, with return to normal at later time points. The ratio of TXA2/PGI2 was significantly higher than control at 30 min and 1 wk. T e synthesis of PGE , PGD2 and PGF was maintained at normal levels throughout the complete course of reperfusion. No changes in eicosanoid synthesis were noted in remote spinal cord regions.

The significant increase of TXA2 synthesis at 5 min and 1 wk of reperfusion may point to a role of this arachidonate metabolite in the acute events and in the later stages of neurological dysfunction. The enhanced release of 5-HETE, a metabolite of 5-HETE, suggest an enhanced formation of leukotriene B4 and peptide leukotrienes and a potential role for these 5-lipoxygerase metabolites of arachidonate in ischemia injury to the brain and the spinal cord.

兔脊髓缺血后血栓素A2和5-HETE生成增加
将家兔脊髓缺血25分钟后进行长时间的再循环。在再循环的不同时间点(5、30分钟、4、18小时和1周),从缺血区域取出切片,在克雷布斯-林格溶液中孵育45分钟。用放射免疫法测定培养液中积累的类二十烷酸、PGE2、PGD2、PGF2α、TXB2、6-酮- pgf1 α和5-HETE的水平。在再灌注早期(5分钟)和晚期(1周),TXB2释放增加。再灌注后5分钟5- hete的释放增加了7倍,并在再循环后18小时和1周保持升高。PGI2合成酶活性在30分钟时下降40%,随后恢复正常。在30min和1w时,TXA2/PGI2的比值显著高于对照组。在整个再灌注过程中,PGE、PGD2和PGF2α的合成维持在正常水平。远端脊髓区域的类二十烷酸合成未见改变。再灌注5分钟和1周时TXA2合成的显著增加可能表明这种花生四烯酸代谢物在急性事件和后期神经功能障碍中的作用。5-HETE (5-HETE的代谢物)的释放增强表明白三烯B4和肽白三烯的形成增强,花生四烯酸5-脂氧合酶代谢物在脑和脊髓缺血损伤中可能起作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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