实验大鼠颅眶联合损伤后依达拉奉对其视神经的保护作用

Protective Effects of Edaravone on the Optic Nerve after Experimental Cranio-orbital Injury in Rats

目的:探讨实验性大鼠颅眶联合损伤(cranio-orbital injury,COI)后视神经损伤机制及依达拉奉的保护作用。方法:144只清洁级SD大鼠,雌雄各半,随机分为对照组、损伤组和治疗组,每组48只。损伤组和治疗组大鼠利用液压冲击颅脑损伤仪建立颅眶联合伤模型,治疗组造模以后腹腔注射依达拉奉30 mg·kg-1,每日2次,共14日。3组分别在造模后3、6、10、14 d取视网膜组织,检测视网膜神经节细胞(retinal ganglion cells,RGCs)活性氧(reactive oxygen species,ROS)含量及不同时间点RGCs凋亡率,光镜下观察视网膜HE染色微观结构,共聚焦显微镜下观察RGCs的TUNEL荧光标记凋亡情况。结果:造模后损伤组RGCs的ROS含量逐渐升高,第10天达到高峰,RGCs凋亡率变化趋势与此相一致,与对照组及治疗组差异有统计学意义(P<0.05),治疗组与对照组相比较无明显差异。光镜下损伤组视网膜结构紊乱,损伤组RGCs的TUNEL荧光标记阳性率明显高于其余两组。结论:COI后RGCs的ROS含量明显升高,导致细胞出现凋亡失调。依达拉奉通过清除ROS逆转这一病理过程,具有明确的视神经保护作用,值得临床推广。

Objective: To investigate the mechanism of optic nerve injury and protective effects of edaravone on rats with experimental cranio-orbital injury(COI). Methods: A total of 144 rats(clean grade)were randomly divided into control group, injury group and treatment group, with 48 rats in each group.The animal model of COI was established in the left eyes of rats of injury and treatment groups by a fluid percussion brain injury(FPI) device. Edaravone(30 mg·kg-1) diluted with normal saline was injected intraperitoneally to the rats of treatment group after modeling every 12 hours for 14 days. Rat retina was obtained at 3, 6, 10 and 14 day, respectively, after injury, to check the content of reactive oxygen species(ROS) in retinal ganglion cells(RGCs) and the apoptosis rate of RGCs. The HE stained microstructure of RGCs was observed under an optical microscope. The TUNEL fluorescence labeled apoptosis of RGCs was observed under a laser confocal microscope. Results: The content of ROS as well as the apoptosis rate of RGCs increased gradually and reached maximum in 10 days after modeling in the injury group. There were statistically significant differences between the injury group and the other two groups(P<0.05). The retina structure of the injury group was disorganized after injury. The positive rate of TUNEL fluorescence labeled RGCs in the injury group was significantly higher than the other two groups. Conclusion: The content of ROS in RGCs increased significantly after COI, resulted in apoptosis imbalance of RGCs. Edaravone prevents this pathological process by eliminating ROS and thus has a protective effect on optic nerve, which is worthy of clinical promotion.