依达拉奉对急性一氧化碳中毒大鼠脑组织超微结构及抗氧化因子表达的影响  

Effects of edaravone on the changes in the ultrastructure of brain tissue and the expressions of antioxidant factor in rats after acute CO poisoning

作　　者：李琴[1] 毕明俊[1] 康海[1] 刘媛媛[1] 邹勇[2] 程永梅[1] 

机构地区：[1]青岛大学医学院附属烟台毓璜顶医院急救中心,山东省烟台264000 [2]青岛大学医学院附属烟台毓璜顶医院中西医结合病房,山东省烟台264000

出　　处：《中华航海医学与高气压医学杂志》2015年第5期341-346,共6页Chinese Journal of Nautical Medicine and Hyperbaric Medicine

摘　　要：目的 观察急性一氧化碳（CO）中毒后大鼠脑组织超微结构及血红素加氧酶-1（HO-1）和核转录因子红细胞2相关因子-2（NRF-2）表达的变化,探讨依达拉奉对中毒后脑损伤的神经保护作用.方法 按文献建立急性CO中毒的动物模型,用透视电镜观察CO中毒后大鼠脑组织超微结构变化,TUNEL染色法检测大鼠脑组织细胞凋亡.免疫组化和免疫荧光双标法检测依达拉奉给药前后大鼠脑组织HO-1和NRF-2的表达变化.结果 CO中毒可引起大鼠脑组织超微结构改变,主要表现为：细胞核内染色质凝聚固缩,细胞质溶解,胞浆内细胞器溶解消失.依达拉奉能明显改善CO中毒后大鼠脑组织超微结构损伤.CO中毒可诱发神经细胞凋亡.随着中毒时间的延长,CO中毒组大鼠脑组织凋亡细胞逐渐增多,但皮质区和纹状体区凋亡细胞数比较差异无统计学意义（P＞0.05）.依达拉奉给药后大鼠脑组织凋亡细胞明显减少,A值也相对降低.HO-1和NRF-2蛋白在正常大鼠脑组织中可见少量表达.CO中毒后两者的表达水平逐渐增加,在皮质区的表达略高于纹状体区,依达拉奉给药后这2种蛋白的表达水平发生变化.结论 依达拉奉可改善中毒后脑组织超微结构损伤,通过抑制神经细胞凋亡,上调HO-1/NRF-2表达,进而对急性CO中毒后脑损伤发挥重要的神经保护作用.Objective To observe changes in the ultrastructure and heme oxygenase-1 （HO-1） /nuclear factor erythrocyte 2-related factor 2 （NRF-2） expressions after acute CO poisoning and also to investigate the protective effects of edaravone on neural systems after acute carbon monoxide （CO） poisoning.Methods The rat model of CO poisoning was established through exposure to CO in the hyperbaric chamber.Changes in the ultrastructure of the rat brain tissue were closely observed by transmission electron microscopy （TEM）.TUNEL stain was used to detect apoptosis of brain cells in rats.Immunohistochemistry and immunofluorescence double stain were used to evaluate the expression levels of heme HO-1/ and NRF-2.Results CO poisoning could induce changes in the ultrastructure of the brain tissue.The main manifestations were chromatin condensation, cytoplasm dissolution and cell organellae decomposition.Edaravone could evidently alleviate damage to the ultrastructure of the brain tissue following CO poisoning.CO poisoning could induce apoptosis, and with the extension of poisoning time, the number of apoptotic cells gradually increased,reached peak at day 7.Seven days after CO poisoning, the absorbance （A） value was as high as in the poisoning group.No significant difference was found between cortex and striatum in the same group （P 〉0.05）.Following edaravone treatment, the number of neural apoptosis was significantly decreased, and statistical significance could be noted, as compared with the values of the poisoning group at the same time points （P 〈 0.01）.Basal expressions of HO-1 and NRF-2 proteins were found in normal brain tissue.The protein expression levels of HO-1 and NRF-2 were gradually increased after CO poisoning, and the expression level in cortex was slightly higher than that in striatum.After treatment with Edaravone, the expressions of HO-1 and NRF-2 were obviously increased, with statistical significance, as compared with those of the poisoning group （P 〈 0.01）.Conclusions Edaravo

关 键 词：一氧化碳中毒 依达拉奉 超微结构 细胞凋亡 氧化应激损伤 血红素加氧酶-1(HO-1) 核转录因子红细胞2相关因子-2(NRF-2) 大鼠 

分 类 号：R595.1[医药卫生—内科学]