神经生长因子对视网膜缺血再灌注损伤中凋亡相关基因c-fos/c-jun表达的影响

Effect of nerve growth factor on expression of apoptosis-related genes in retinal ischemia-reperfusion injury

目的探讨神经生长因子（NGF）对视网膜缺血再灌注损伤中凋亡相关基因c—fos／c—jun表达的影响。方法将28只Wistar大鼠随机分为正常组、缺血组和治疗组，后两组又按照不同再灌注时间分为再灌注后1、6、12、24、48、72h6个时间段。建立视网膜缺血再灌注损伤动物模型，以NGF或平衡盐溶液玻璃体腔注射，通过免疫组织化学法检测各组视网膜组织中c-fos／c-jun基因的表达变化。结果缺血组视网膜再灌注后1h可发现有c—fos／c-jun蛋白的表达，12h达到高峰，24h表达明显下降。治疗组变化规律与缺血组相似，但表达量明显减弱，再灌注1～24h各时段差异有统计学意义（P〈0．05）。结论视网膜缺血再灌注损伤时c—fos／c-jun基因在视网膜神经节细胞层（RGCL）与内核层表达增高；NGF可以抑制视网膜缺血再灌注损伤时c—fos／c-jun基因在视网膜的表达。

Objective Retinal ischemia-reperfusion injury is a common pathologic process in ophthalmology,which lead to the serious damage of visual function. Apoptosis is one of most common patterns of the retinal ganglion cells death in retinal ischemia-reperfusion injury. The aim of this paper was to explore the effect of nerve growth factor （NGF） on the expression of apoptosis-related genes c-fos/c-jun in retinal ischemia-reperfusion injury. Methods The model of experimental retinal ischemia-reperfusion injury was established by puncture of anterior chamber and increasing tension. Twenty-eight Wistar rats were divided into normal group（4 rats） , ischemia group（ 24 left eyes）and treatment group （24 right eyes）randomly, and the latter two groups were assigned to 6 subgroups averagely according to the time points after reperfusion： 1 hour,6,12,24,48, and 72 hours groups. 10 μL NGF or 10 μL balance saline solution was intravitreously injected after reperfusion in the left eyes of treatment group or right eyes of model groups, respectively. The expression of c-fos/c-jun was quantitatively detected by SABC immunohistochemistry. Results No positive expression of c-fos/c-jun was found in retina of normal control group. In ischemia group,the c-fos/c-jun was expressed mainly in retinal ganglion cells 1 hour after reperfusion,reached peak at the 12 nd hour and decreased obviously at the 24 th hour. In the treatment group, the change trend of c-fos/c-jun was similar to that of ischemia group with the less expression of c-fos/c-jun. There was statistical significance in the expression of c-fos/c-jun between the ischemia and treatment group in 1 - 24 hours after reperfusion（ P 〈 0.05）. Conclusion The c-fos/c-jun may be involved in the mechanisms of retinal ischemia-reperfusion injury by playing role in apoptosis. NGF may have the therapeutic effect on retinal ischemia- reperfusion injury by inhibiting the increase of expression of c-fos/c-jun in retinal ischemia-reperfusion injury.