Tyurin V A, Tyurina Y Y, Borisenko G G, Sokolova T V, Ritov V B, Quinn P J, Rose M, Kochanek P, Graham S H, Kagan V E
Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania 15238, USA.
J Neurochem. 2000 Nov;75(5):2178-89. doi: 10.1046/j.1471-4159.2000.0752178.x.
Oxidative stress may contribute to many pathophysiologic changes that occur after traumatic brain injury. In the current study, contemporary methods of detecting oxidative stress were used in a rodent model of traumatic brain injury. The level of the stable product derived from peroxidation of arachidonyl residues in phospholipids, 8-epi-prostaglandin F(2alpha), was increased at 6 and 24 h after traumatic brain injury. Furthermore, relative amounts of fluorescent end products of lipid peroxidation in brain extracts were increased at 6 and 24 h after trauma compared with sham-operated controls. The total antioxidant reserves of brain homogenates and water-soluble antioxidant reserves as well as tissue concentrations of ascorbate, GSH, and protein sulfhydryls were reduced after traumatic brain injury. A selective inhibitor of cyclooxygenase-2, SC 58125, prevented depletion of ascorbate and thiols, the two major water-soluble antioxidants in traumatized brain. Electron paramagnetic resonance (EPR) spectroscopy of rat cortex homogenates failed to detect any radical adducts with a spin trap, 5,5-dimethyl-1-pyrroline N:-oxide, but did detect ascorbate radical signals. The ascorbate radical EPR signals increased in brain homogenates derived from traumatized brain samples compared with sham-operated controls. These results along with detailed model experiments in vitro indicate that ascorbate is a major antioxidant in brain and that the EPR assay of ascorbate radicals may be used to monitor production of free radicals in brain tissue after traumatic brain injury.
氧化应激可能导致创伤性脑损伤后发生的许多病理生理变化。在当前研究中，在创伤性脑损伤的啮齿动物模型中使用了当代检测氧化应激的方法。磷脂中花生四烯酰残基过氧化产生的稳定产物8-表前列腺素F（2α）的水平在创伤性脑损伤后6小时和24小时升高。此外，与假手术对照组相比，创伤后6小时和24小时脑提取物中脂质过氧化荧光终产物的相对量增加。创伤性脑损伤后，脑匀浆的总抗氧化储备、水溶性抗氧化储备以及组织中抗坏血酸、谷胱甘肽和蛋白质巯基的浓度均降低。环氧化酶-2的选择性抑制剂SC 58125可防止创伤性脑损伤中两种主要水溶性抗氧化剂抗坏血酸和硫醇的消耗。大鼠皮质匀浆的电子顺磁共振（EPR）光谱未能检测到与自旋捕获剂5,5-二甲基-1-吡咯啉N-氧化物的任何自由基加合物，但确实检测到了抗坏血酸自由基信号。与假手术对照组相比，创伤性脑损伤样本来源的脑匀浆中抗坏血酸自由基EPR信号增加。这些结果以及详细的体外模型实验表明，抗坏血酸是脑中的主要抗氧化剂，抗坏血酸自由基的EPR测定可用于监测创伤性脑损伤后脑组织中自由基的产生。
