Lucas J H, Wheeler D G, Emery D G, Mallery S R
Department of Physiology, College of Medicine, Ohio State University, Columbus 43210, USA.
J Neuropathol Exp Neurol. 1998 Oct;57(10):937-54. doi: 10.1097/00005072-199810000-00006.
Glutathione is part of the system of cellular defenses against lipid peroxidation and other free radical-mediated damage. An established in vitro trauma model was utilized to evaluate whether glutathione is a factor in the survival of mammalian spinal cord neurons following physical injury. Cultured murine spinal neurons were subjected to a standard lesion: transection of a primary dendrite 100 microm from the perikaryon. Prior reduction of glutathione with ethacrynic acid or buthionine sulfoximine caused a dose-dependent decrease in neuronal survival 24 hours after dendrotomy. Prior glutathione augmentation with gamma-glutamylcysteine or L-2-oxo-4-thiazolidine carboxylic acid significantly increased survival, but N-acetyl-cysteine was not protective. Gamma glutamylcysteine effected the most rapid increase in glutathione (peak at 10 min), and survival was 72% +/- 10 when 0.2 mM gamma-glutamylcysteine was added immediately after dendrotomy compared with 38% +/- 4 in the control group (p < 0.0001). These results indicate that the level of glutathione is a factor in spinal cord neuron survival after physical trauma, and that glutathione augmentation may be an effective acute phase spinal cord injury (SCI) intervention strategy.
谷胱甘肽是细胞防御脂质过氧化和其他自由基介导损伤系统的一部分。利用已建立的体外创伤模型来评估谷胱甘肽是否是物理损伤后哺乳动物脊髓神经元存活的一个因素。将培养的小鼠脊髓神经元进行标准损伤：在距胞体100微米处切断一根初级树突。事先用依他尼酸或丁硫氨酸亚砜胺降低谷胱甘肽水平，导致树突切断术后24小时神经元存活率呈剂量依赖性下降。事先用γ-谷氨酰半胱氨酸或L-2-氧代-4-噻唑烷羧酸增加谷胱甘肽水平可显著提高存活率，但N-乙酰半胱氨酸没有保护作用。γ-谷氨酰半胱氨酸使谷胱甘肽增加最为迅速（10分钟时达到峰值），在树突切断术后立即加入0.2 mMγ-谷氨酰半胱氨酸时，存活率为72%±10%，而对照组为38%±4%（p<0.0001）。这些结果表明，谷胱甘肽水平是物理创伤后脊髓神经元存活的一个因素，增加谷胱甘肽水平可能是一种有效的急性脊髓损伤（SCI）干预策略。
