INCREASED PRODUCTION OF EICOSANOIDS, TXA2, PGI2 AND LTC4 IN EXPERIMENTAL SPINAL-CORD INJURIES
INCREASED PRODUCTION OF EICOSANOIDS, TXA2, PGI2 AND LTC4 IN EXPERIMENTAL SPINAL-CORD INJURIES
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DOI：
10.1038/sc.1994.84
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发表时间：
1994-08-01
期刊：
影响因子：
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通讯作者：
KATOH, S
中科院分区：
文献类型：
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作者：
MITSUHASHI, T;IKATA, T;KATOH, S
花生四烯酸代谢产物具有多种生物活性。血栓素A_2（TXA_2）刺激血小板聚集和血管收缩，而前列腺素I_2（PGI_2）拮抗其活性。测定生物材料中的血栓素B2（TXB 2）和6-酮-前列腺素F1 α（6-keto-PGF 1 α）。本文用放射免疫分析法测定了实验性脊髓损伤动物血浆血栓素B_2（TXB_2）、6-酮-前列腺素F_（1 α）和白三烯C_4（LTC_4）的含量。伤后5分钟，大鼠脊髓中TXB_2达峰值浓度133.6 ± 3.8 pmol/g脊髓，6-keto-PGF_（1 α）达峰值浓度26.2 ± 11.7 pmol/g脊髓。TXB 2的产生与荧光素摄取监测的血管损伤之间有很好的相关性。当在损伤前10分钟给予选择性抑制TXA 2合成酶活性的OKY-046（（E）-3-[4-（1-咪唑甲基）苯基]-2-丙烯酸）时，TXB 2产生的增加被抑制80%以上，但血管损伤程度仅降低40%。在豚鼠脊髓中，在压迫后10分钟，LTC 4水平达到峰值浓度2.2 +/- 0.4 pmol/g脊髓，而TXB 2达到146.8 +/- 6.2 pmol/g脊髓。TXB_2的增加与压迫程度有关，而LTC_4的增加与压迫程度无关。这些结果表明，血管活性类花生酸，TXA_2，PGI_2和LTC_4，在脊髓损伤后的继发性损害中发挥重要作用，虽然它们的作用可能是不同的动物物种。
Arachidonate metabolites have many kinds of bioactivities. Thromboxane A2 (TXA2) stimulates platelet aggregation and vasoconstriction, whereas prostaglandin I2 (PGI2) antagonises its activities. Thromboxane B2 (TXB2) and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) are determined in biological materials. Production of TXB2, 6-keto-PGF1alpha and leukotriene C4 (LTC4), which have potent vascular permeability, was measured by radioimmunoassay in experimental spinal cord injured animals. TXB2 level in the rat spinal cord reached a peak concentration of 133.6 +/- 3.8 pmol/g cord, and 6-keto-PGF1alpha increased to 26.2 +/- 11.7 pmol/g cord 5 minutes after the injury. There was good correlation between TXB2 production and vascular damage as monitored by fluorescein uptake. When OKY-046 ((E)-3-[4-(1-imidazolylmetyl) phenyl]-2-propenoic acid), which selectively inhibits TXA2 synthetase activity, was administered 10 minutes before injury, the increase in TXB2 production was inhibited by more than 80%, but the degree of vascular damage was reduced by only 40%. In the guinea pig spinal cord, LTC4 levels reached a peak concentration of 2.2 +/- 0.4 pmol/g cord 10 minutes after compression, while that of TXB2 reached 146.8 +/- 6.2 pmol/g cord. The increased production of TXB2 was correlated with the degree of compression injury while that of LTC4 production did not. These findings suggest that vasoactive eicosanoids, TXA2, PGI2 and LTC4, play important roles in secondary damage following spinal cord injury, although their roles may be different among species of animals.