依达拉奉对少突胶质细胞放射性反应的保护作用研究

Protective effects of edaravone on the radiation response of oligodendrecyte in rats following whole brain irradiation

目的观察大鼠单次全脑照射后脑内少突胶质谱系细胞的变化，以及新型自由基清除剂依达拉奉对少突胶质细胞放射性反应的影响。方法将雄性SD大鼠120只随机分为假照射组、照射组、依达拉奉组。采用10Gy单次全脑照射模型，制模后依达拉奉组大鼠分别按剂量0．3、1．0和3．0mg／kg依达拉奉腹腔注射；构建放射性脑损伤大鼠脑组织芯片，用免疫组织化学法检测皮质A285、少突胶质细胞表面标志物4（O4）、2’，3＇-环磷核苷酸水解酶（CNPase）蛋白表达变化。结果与假照射组比较，照射后1d皮质A285阳性细胞数目即开始增多，照射后1周最多（P〈0．01），1个月时差异无统计学意义；而O4与CNPase阳性细胞数在照射后1d时显著减少，以O4阳性细胞数减少为甚（P〈0．01），1周后差异无统计学意义。与照射组比较，依达拉奉干预后A285阳性细胞数有不同程度减少，O4、CNPase阳性细胞数有不同程度增加（1．0mg／kg，P〈0．05；3．0mg／kg，P〈0．01）。结论大鼠全脑照射后脑皮质少突胶质前体细胞反应性增多，呈时程性变化；一定剂量的依达拉奉对少突胶质细胞放射性反应有保护作用，呈现剂量依赖性。

Objective To investigate the changes of the oligodendrocyte lineage cells in the cortex following whole brain irradiation and the effects of the neotype free radical scavenger, edaravone on radiation response of oligodendrocyte in rats. Methods 120 male Sprague Dawley rats were randomly divided into shamirradiation group, irradiation group and edaravone group. The model of whole-brain irradiation was established with exposure of the whole brain of the rats to 4 MeV X-rays with a single-dose of 10 Gy. The rats were injected intrapefitoneally with edaravone at 0.3,1.0 and 3.0 mg/kg. Tissue microarray of irradiation-induced brain injury in rats was constructed. The expression of A2B5, oligodendrocyte marker 4（O4） and 2＇ ,3＇-cyclic nucleotide 3＇- phosphodiesterase （ CNPase ） in the cortex was examined by tissue microarray technology and immunohistochemistry. The positive cells were counted. Results Compared with the sham-irradiation group, the number of A2B5-positive cells increased and the number of O4, CNPase-positive cells decreased significantly at certain time in the irradiation group（ P 〈 0.05）. Compared with irradiation group, A2B5-positive cells decreased significantly after edaravone treatment, while O4-positive cells and CNPase-positive cells increased significantly （ P 〈 0.05, or P 〈 0.01 ） . Conclusions The number of oligodendrocyte precursor cells in the cortex of rats increased reactively following whole brain irradiation and changed with time. Edaravone played a protective role in oligodendroeyte ischemie reaction in a dose-dependent manner.