rhEPO对视网膜缺血再灌注损伤大鼠视网膜神经细胞凋亡及Fas、FADD表达的影响

Effect of rhEPO on apoptosis and Fas,FADD expression of retina neuron in rats with ischemic-reperfusion injury

目的探讨重组人促红细胞生成素（rhEPO）对视网膜缺血再灌注损伤（RIRI）所致视网膜神经细胞凋亡的保护作用及机制。方法将52只Wistar大鼠随机分为对照组4只，不行特殊处理；模型组和观察组各24只，均通过前房穿刺加压法制成RIRI模型，并分别于缺血前24h腹腔注射生理盐水和rhEPo，于1～72h应用末端脱氧核酸转移酶介导的脱氧三磷酸尿苷缺口末端标记（TUNEL）法检测视网膜神经细胞凋亡，采用过氧化物酶标记的sP免疫组化方法检测Fas、Fas相关蛋白（FADD）表达。结果对照组未见细胞凋亡及Fas、FADD表达。观察组与模型组视网膜神经细胞凋亡及Fas、FADD表达均出现于再灌注后6h，24h达到高峰，48h开始下降，其中观察组细胞凋亡在12、24、48h明显低于模型组（P〈0．05），Fas、FADD表达在6、12、24h明显低于模型组（P〈0．05）。结论rhEPO可明显减轻RIRI所致大鼠视网膜神经细胞凋亡，可能机制为下调Fas、FADD表达。

Objective To investigate the therapeutic effect of recombinant human erythropoietin （rhEPO） on apoptosis of retinal neuron induced by retinal ischemia/reperfusion injury （RIRI） and its mechanisms. Methods 52 Wistar rats were randomly divided into 3 groups ,the control group were treated with no especial measures. The observed group and the model group were made models of retinal RIRI by increasing the intraocular pressure, rhEPO and normal saline were intravitreoualy injected respectively 24hours before that. Apoptotic cells were determined by TUNEL method,and the expressions of Fas and FADD protein were determined by SP immunohistoehemistry. Results No apoptotie cells and expression of Fas and FADD protein were found in the control group. Apoptotic cells in the other two groups were expressed at 6 hour after reperfusion in the retina, peaked at the 24 hour, and decreased at the 48 hour. The number of apoptotic cells in the observed group were significantly lower than that in the medal group at 12, 24 and 48 hour （P 〈 0.05） , and the expression of Fas, FADD protein were significantly lower than those in the model group at 6, 12 and 24 hour （P 〈0.05）. Conclusion rhEPO can obviously decrease the apoptosis induced by retinal RIRI , possible mechanism may be down-regulate the Fas and FADD expression.