法舒地尔在大鼠视神经损伤后的保护作用研究

摘要

Objective To investigate the protective effect of Fasudil after the optic nerve injury.Methods Sixty healthy male SD rats were randomly divided into three groups.They were normal group with 12 rats (24 eyes),control group with 24 rats (24 eyes) and Fasudil treatment group with 24 rats (24 eyes).The rats in normal group did not receive any treatment and the rats in treatment group and control group underwent forceps clamping to establish right eye optic nerve injury model.Then the rats in the two experimental groups were injected with 10 mg/kg of Fasudil and an equal dose of saline respectively.The rats were executed at 3,7,14 and 21 days after injury.The number and morphology changes of RGCs were observed through Hematoxylin Eosin staining of retinal tissue,and the average optical density (AOD) value of HIF-1α were tested by computer image analysis.Results The morphology and edema of cells in different retinal layers under light microscope significantly improved in treatment group compared with that in control group.The number of RGCs in treatment group was higher than that in control group,and the differences were statistically significant (t =13.132-18.933,P ＜ 0.05).The AOD values and positive cells counts in immunohistochemical chromosomes showed the HIF-1 α expression level in treatment group was significantly lower than that in control group,and the differences were statistically significant (t =11.203-23.522,P ＜ 0.05).Conclusion Fasudil can inhibit the upregnlation of HIF-1α expression,reduce the damage of RGCs,and plays a protective role in the optic nerve after injury.%目的 探讨视神经损伤后法舒地尔(Fasudil)的保护作用.方法 选取60只健康雄性SD大鼠,随机分为3组:正常组12只(24只眼),对照组24只(生理盐水组)(24只眼),治疗组24只(法舒地尔组)(24只眼).正常组不做任何处理,治疗组和对照组行视神经钳夹法建立右眼视神经不完全损伤模型,然后分别行腹腔注射10 mg/kg法舒地尔注射液和等容量的生理盐水.在损伤后3、7、14、21 d摘除眼球,制备视网膜切片,光镜下观察视网膜神经节细胞(RGCs)形态和数量的变化,并进行免疫组织化学染色以计算机图像分析技术半定量检测视网膜组织中缺氧诱导因子-1α(HIF-1α)的平均光密度值(AOD).结果 光镜下观察各时间段治疗组视网膜各层细胞的形态和水肿程度较对照组轻,且RGCs数量较对照组高,差异有统计意义(t=13.132～18.933,P＜0.05).相同时间段免疫组化染色的AOD值及阳性细胞计数显示治疗组HIF-1α表达均弱于对照组,差异有统计意义(t=11.203～23.522,P＜0.05).结论 在视神经损伤后法舒地尔可以抑制HIF-1α表达的上调,降低RGCs的损伤,从而发挥对视神经的保护作用.