重组人促红细胞生成素对大鼠视神经损伤的神经保护作用。
Neuroprotective effect of recombinant human erythropoietin on optic nerve injury in rats.
机构信息
Department of Ophthalmology, First Hospital of China Medical University, Shenyang, Liaoning 110001, China.
出版信息
Chin Med J (Engl). 2009 Sep 5;122(17):2008-12.
BACKGROUND
Optic nerve injury, caused by retinal and optic nerve diseases, can eventually result in vision loss. To date, few effective treatments have been discovered to restore visual function. Previous studies showed that recombinant human erythropoietin (rhEPO) has a neuroprotective effect on the central nervous system, particularly in nerve injury. In this study, we investigated the effects of rhEPO on axonal regeneration and functional restoration following optic nerve injury. This was done by measuring the expression of growth associated protein 43 (GAP-43), a marker for neuronal regeneration, on the retina and flash-visual evoked potential (F-VEP).
METHODS
Adult Wistar rats were randomly assigned to rhEPO and control (saline) groups. Optic nerve crush injury models were established and rhEPO or saline were immediately injected into the vitreous cavity. The expression of GAP-43 was detected by immunohistochemistry and the F-VEP was measured pre-injury, immediately after injury, 1 week and 2 weeks post-injury.
RESULTS
No detectable staining for GAP-43 was observed in normal retina. In the control group, the level of GAP-43 expression was higher at 1 week post-injury, but decreased at 2 weeks. In the rhEPO group, the level of GAP-43 expression was notably higher at both 1 week and 2 weeks. At each time point post-injury, the expression of GAP-43 in rhEPO group was significantly higher than the control group (P < 0.05). Obvious changes in F-VEP examination were detected immediately after optic nerve injury, including significantly prolonged latency and decreased amplitude of the P1 wave. In the control group, the changes were still obvious at 1 week. The latency was decreased and the amplitude had slightly recovered to 28.23% of the normal value at 2 weeks. In rhEPO group, there was significantly more recovery than the control group at 1 week and 2 weeks post-injury (P < 0.05). The latency most close to the normal level and the amplitude had recovered to 65.51% of the normal value at 2 weeks.
CONCLUSIONS
rhEPO can prolong the expression of GAP-43 and increase its intensity after optic nerve injury, thereby promoting neural repair and axonal regeneration. Under the protection of rhEPO, the conduction velocity of the optic nerve recovered significantly. Therefore, rhEPO has neuroprotective effects on the optic nerve and promotes functional restoration of the optic nerve.
背景
视网膜和视神经疾病引起的视神经损伤最终会导致视力丧失。迄今为止，发现很少有有效的治疗方法可以恢复视觉功能。先前的研究表明，重组人促红细胞生成素（rhEPO）对中枢神经系统具有神经保护作用，尤其是在神经损伤方面。在这项研究中，我们研究了 rhEPO 对视神经损伤后轴突再生和功能恢复的影响。这是通过测量视网膜和闪光视觉诱发电位（F-VEP）上生长相关蛋白 43（GAP-43）的表达来实现的，GAP-43 是神经元再生的标志物。
方法
成年 Wistar 大鼠被随机分配到 rhEPO 和对照组（生理盐水）。建立视神经挤压伤模型，并立即向玻璃体腔注射 rhEPO 或生理盐水。通过免疫组织化学检测 GAP-43 的表达，在损伤前、损伤后 1 周和 2 周测量 F-VEP。
结果
正常视网膜中未检测到 GAP-43 的可检测染色。在对照组中，损伤后 1 周时 GAP-43 的表达水平较高，但在 2 周时降低。在 rhEPO 组中，1 周和 2 周时 GAP-43 的表达水平明显更高。在每个损伤后时间点，rhEPO 组中 GAP-43 的表达均明显高于对照组（P < 0.05）。视神经损伤后 F-VEP 检查明显变化，包括 P1 波潜伏期明显延长，波幅降低。在对照组中，1 周时仍很明显。潜伏期缩短，波幅在 2 周时恢复至正常值的 28.23%。在 rhEPO 组中，1 周和 2 周时的恢复明显多于对照组（P < 0.05）。潜伏期最接近正常水平，波幅恢复至正常值的 65.51%。
结论
rhEPO 可延长视神经损伤后 GAP-43 的表达并增加其强度，从而促进神经修复和轴突再生。在 rhEPO 的保护下，视神经的传导速度明显恢复。因此，rhEPO 对视神经具有神经保护作用，并促进视神经功能恢复。
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