Tissue factor pathway inhibitor protects the ischemic spinal cord.
Tissue factor pathway inhibitor protects the ischemic spinal cord.
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组织因子途径抑制剂可保护缺血性脊髓。
DOI：
10.1006/jsre.1996.0243
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
S. Money
中科院分区：
文献类型：
--
作者：
B. Koudsi;D. Chatman;B. Ballinger;E. W. Ferguson;B. Kraemer;G. A. Miller;T. Wun;G. Farr;S. Money
组织因子途径抑制剂 (TFPI) 是一种新型药物，可与组织因子/VIIa 复合物和 Xa 因子结合，从而减少组织因子 (TF) 对炎症和外在凝血途径的影响。我们假设 TFPI 全身治疗可能会限制缺血再灌注 (IR) 损伤。我们的实验旨在评估 TFPI 对脊髓 IR 的影响。二十三只成年新西兰白兔的主动脉周围放置了圈套闭塞装置，并通过隧道到达皮下位置。 48小时后，在完全清醒的状态下，动物用TFPI（1毫克/千克推注，然后1小时输注20微克/千克/分钟）或肝素（100 U/kg推注），然后1小时输注10毫升/千克/小时的PBS进行治疗，而对照接受磷酸盐缓冲盐水（20毫升，然后1小时输注10微克/千克/分钟）。毫升/公斤/小时）。通过圈套器装置将所有组的肾下主动脉闭塞21分钟。观察动物3天，并根据Tarlov标准对神经功能恢复进行分级。结果以后肢恢复的动物百分比进行评估（Tarlov 3 和 4）。闭塞后 24 小时，88% 的 TFPI 治疗动物恢复了神经功能，而肝素治疗组和磷酸盐缓冲盐水组中只有 20% 和 10% 恢复了神经功能（P 分别为 0.031 和 0.009）。 72小时时，63%的TFPI动物保留了神经功能，而肝素处理的动物为20%，磷酸盐缓冲盐水处理的动物为10%（P=0.032，TFPI与磷酸盐缓冲盐水相比）。 TFPI 的作用机制尚不完全清楚，但该药物可能有望预防脊髓 IR 损伤。
Tissue factor pathway inhibitor (TFPI) is a novel agent that binds to tissue factor/VIIa complex and factor-Xa, thereby reducing the effect of tissue factor (TF) on inflammation and the extrinsic pathway of coagulation. We hypothesize that systemic treatment with TFPI may limit ischemia-reperfusion (IR) injury. Our experiment was designed to evaluate the effects of TFPI on IR in the spinal cord. Twenty-three adult New Zealand white rabbits had snare occlusion devices placed circumferentially around the aorta and tunneled to a subcutaneous position. Forty-eight hours later, in the fully awake state, the animals were treated with either TFPI (1 mg/kg bolus followed by a 1-hr infusion of 20 microgram/kg/min), or heparin (100 U/kg bolus) followed by a 1-hr infusion of 10 ml/kg/hr of PBS while controls received phosphate buffered saline (20 ml followed by a 1-hr infusion of 10 ml/kg/hr). The infrarenal aorta was occluded for 21 min in all groups via the snare device. Animals were observed for 3 days and neurologic recovery was graded by the Tarlov criteria. Results were evaluated as percent of animals with hindlimb recovery (Tarlov 3 and 4). At 24 hr postocclusion, 88% of the TFPI-treated animals had recovered neurologic function versus only 20% of heparin-treated animals and 10% of the phosphate buffered saline group (P=0.031 and 0.009, respectively). At 72 hr, 63% of the TFPI animals retained neurologic function versus 20% of heparin-treated animals and 10% of phosphate buffered saline-treated animals (P=0.032, TFPI versus phosphate buffered saline). The mechanism of action of TFPI is not completely understood, yet this drug may hold promise in the prevention of IR injury of the spinal cord.