Ohtsuki T, Matsumoto M, Kuwabara K, Kitagawa K, Suzuki K, Taniguchi N, Kamada T
First Department of Internal Medicine, Osaka University Medical School, Japan.
Brain Res. 1992 Dec 25;599(2):246-52. doi: 10.1016/0006-8993(92)90398-s.
We investigated whether reversible oxidative stress induced by the administration of the superoxide dismutase inhibitor, diethyldithiocarbamate, could induce tolerance to subsequent cerebral ischemia in gerbil hippocampal neurons. Mature male gerbils received intraperitoneal injections of diethyldithiocarbamate (1.0 g/kg), which led to reduced superoxide dismutase activity and increases in thiobarbituric acid-reactive substance in the brain. Cerebral ischemia was produced by occluding the bilateral common carotid arteries for 5 min, either 2 or 4 days after diethyldithiocarbamate injection. One week after ischemia, samples from each brain were stained with hematoxylin-eosin to evaluate ischemic neuronal damage in the hippocampal CA1 sector. Diethyldithiocarbamate treatment 4 days before ischemia had significant protective effects against cerebral ischemia, while diethyldithiocarbamate 2-day pretreatment and vehicle treatment failed to show neuroprotection. Biochemical examinations showed a clear induction of heat shock protein 72 and a significant increase in manganese-containing superoxide dismutase in the hippocampus in animals treated with diethyldithiocarbamate 4 days prior to ischemia. These results suggested that the oxidative stress caused by diethyldithiocarbamate could induced tolerance to ischemia in the gerbil brain, and that the increase in the biosynthesis of manganese-containing superoxide dismutase and heat shock protein 72 could provide a biochemical explanation of the tolerance induced under these conditions.
我们研究了通过给予超氧化物歧化酶抑制剂二乙二硫代氨基甲酸盐诱导的可逆性氧化应激是否能诱导沙土鼠海马神经元对随后脑缺血的耐受性。成年雄性沙土鼠腹腔注射二乙二硫代氨基甲酸盐（1.0 g/kg），这导致大脑中超氧化物歧化酶活性降低，硫代巴比妥酸反应性物质增加。在注射二乙二硫代氨基甲酸盐后2天或4天，通过阻断双侧颈总动脉5分钟来制造脑缺血。缺血1周后，对每个大脑的样本进行苏木精-伊红染色，以评估海马CA1区的缺血性神经元损伤。缺血前4天给予二乙二硫代氨基甲酸盐治疗对脑缺血有显著的保护作用，而二乙二硫代氨基甲酸盐2天预处理和溶剂治疗未显示神经保护作用。生化检查显示，在缺血前4天接受二乙二硫代氨基甲酸盐治疗的动物海马中，热休克蛋白72明显诱导，含锰超氧化物歧化酶显著增加。这些结果表明，二乙二硫代氨基甲酸盐引起的氧化应激可诱导沙土鼠脑对缺血的耐受性，含锰超氧化物歧化酶和热休克蛋白72生物合成的增加可为这些条件下诱导的耐受性提供生化解释。
