Promoting glutathione synthesis after spinal cord trauma decreases secondary damage and promotes retention of function
Promoting glutathione synthesis after spinal cord trauma decreases secondary damage and promotes retention of function
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DOI：
10.1096/fj.00-0228com
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发表时间：
2001-01-01
期刊：
影响因子：
4.8
通讯作者：
Juurlink, BHJ
中科院分区：
文献类型：
--
作者：
Kamencic, H;Griebel, RW;Juurlink, BHJ
该研究旨在1）量化T6挤压损伤后脊髓中的氧化应激，2）确定给予原半胱氨酸化合物L-2-氧代噻唑烷-4-羧酸酯（OTC）是否会上调谷胱甘肽（GSH）合成并降低氧化应激，3）确定降低的氧化应激是否会导致更好的组织和功能保留。我们证明，脊髓压迫（5秒，50克动脉瘤夹）在T6大鼠的结果是广泛的氧化应激（在C3和L4的氧化应激显着增加）和快速发作。氧化应激的指标是谷胱甘肽含量，蛋白质羰基含量和谷胱甘肽还原酶的失活。OTC给药导致氧化应激显著降低，与T6时白色物质的保留相关（OTC给药动物中保留16 +/-1.9%，盐水给药动物中保留小于1%）。6周后，对照组、生理盐水处理组和OTC处理组动物的行为指数分别为：角板评分（59度、32度和42度）、改良Tarlov评分（7、2.4和4.1）和Basso-Beattie-Bresnahan评分（21、5.3和12.9）。我们的结论是，管理OTC脊髓创伤后大大降低氧化应激，并允许组织保存，从而使其他截瘫动物的活动。
The study aimed to 1) quantify oxidative stress in spinal cord after crush injury at T6, 2) determine whether the administration of the procysteine compound L-2-oxothiazolidine-4-carboxylate (OTC) would up-regulate glutathione (GSH) synthesis and decrease oxidative stress, and 3) determine whether decreased oxidative stress results in better tissue and function retention. We demonstrate that spinal cord compression (5 s with a 50 g aneurysm clip) at T6 in rats results in oxidative stress that is extensive (significant increases in oxidative stress seen at C3 and L4) and rapid in onset. Indices of oxidative stress used were GSH content, protein carbonyl content, and inactivation of glutathione reductase. Administration of OTC resulted in a marked decrease in oxidative stress associated with a sparing of white matter at T6 (16 +/-1.9% retained in OTC-treated animals vs, less than 1% in saline-treated). Behavioral indices in control, saline-treated, and OTC-treated animals after 6 wk were respectively: angle board scores (59 degrees, 32 degrees, and 42 degrees), modified Tarlov score (7, 2.4, and 4.1), and Basso-Beattie-Bresnahan score (21, 5.3, and 12.9). We conclude that administration of OTC after spinal cord trauma greatly decreases oxidative stress and allows tissue preservation, thereby enabling otherwise paraplegic animals to locomote.