Antithrombin reduces the ischemia/reperfusion-induced spinal cord injury in rats by attenuating inflammatory responses
Antithrombin reduces the ischemia/reperfusion-induced spinal cord injury in rats by attenuating inflammatory responses
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DOI：
10.1160/th03-06-0385
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发表时间：
2004-01-01
影响因子：
6.7
通讯作者：
Kitamura, N
中科院分区：
文献类型：
--
作者：
Hirose, K;Okajima, K;Kitamura, N
抗凝血酶（AT）通过促进前列环素的包膜释放来揭示其抗炎活性。（PGI(2)）。由于神经炎症在缺血/再灌注（I/R）诱导的脊髓损伤（SCI）的发展中起着关键作用，因此AT可能通过减轻炎症反应来减轻I/R诱导的脊髓损伤。我们在本研究中用I/ r诱导的大鼠脊髓损伤模型检验了这种可能性。AT通过抑制运动神经元数量的减少，显著降低脊髓损伤动物的死亡率和运动障碍，再灌注后脊髓微梗死明显减少。AT显著增强了I/ r诱导的脊髓组织中PGI稳定代谢物6-酮- pgf （1 α）水平的升高(2)。AT显著抑制I/ r诱导的脊髓组织tnf - α、大鼠白细胞介素-8和髓过氧化物酶水平的升高。相比之下，Trp（49）修饰的AT没有显示出任何保护作用。吲哚美辛预处理可显著逆转AT的保护作用。Xa因子的一种无活性衍生物，选择性地抑制凝血酶的产生，已被证明不能减少SCI。综上所述，这些观察结果强烈表明，AT可能主要通过促进内皮细胞PGI生成的抗炎作用来减轻I/ r诱导的SCI(2)。这些发现也表明AT可能是一种潜在的神经保护剂。
Antithrombin (AT) reveals its antiinfalammatory activity by promoting enclothelial release of prostacyclin.(PGI(2)) in vivo. Since neuroinflammation is critically involved in the development of ischemia/reperfusion (I/R)-induced spinal cord injury (SCI), it is possible that AT reduces the I/R-induced SCI by attenuating the inflammatory responses. We examined this possibility using rat model of I/R-induced SCI in the present study. AT significantly reduced the mortality and motor disturbances by inhibiting reduction of the number of motor neurons in animals subjected to SCI Microinfarctions of the spinal cord seen after reperfusion were markedly reduced by AT. AT significantly enhanced the I/R-induced increases in spinal cord tissue levels of 6-keto-PGF(1alpha) a stable metabolite of PGI(2). AT significantly inhibited the I/R-induced increases in spinal cord tissue levels of TNF-alpha, rat interleukin-8 and myeloperoxidase. In contrast,Trp(49)modified AT did not show any protective effects. Pretreatment with indomethacin significantly reversed the protective effects of AT. An inactive derivative of factor Xa, which selectively inhibits thrombin generation, has been shown to fail to reduce SCI.Taken together, these observations strongly suggested that AT might reduce I/R-induced SCI mainly by the antiinflammatory effect through promotion of endothelial production of PGI(2.)These findings also suggested that AT might be a potential neuroprotective agent.