近来发现EPO的神经保护作用及促红细胞生成作用具有不同的作用机制和特点，两种作用所需EPO的刺激时间不同，参与作用的受体也不同。研究表明，促红细胞生成需要持续不断的EPO刺激，而神经保护作用仅需要短暂的EPO刺激[32]。据此，可以通过缩短EPO的作用时间，将这两种作用分离。Erbayraktar等[33]将EPO分子中唾液酸基团全部去除生成asialoEPO，其与EPO受体的亲和力不变，但半衰期较普通EPO明显缩短，试验证明，asialoEPO同样具有完全的神经保护作用[34,35]，而不刺激红细胞的生成。asialoEPO虽然半衰期很短，但其与EPO受体的亲和力与普通EPO无区别，仍然不能完全排除刺激骨髓红祖细胞的可能性。根据以往的研究，骨髓中EPO的受体主要是（EPOR）2，属于I类细胞因子家族，参与EPO促红细胞生成的作用。而介导神经保护作用的受体无论在分子量、受体亲和力或蛋白结构上都不同于（EPOR）2[36]，在对EPO构效关系的研究中发现，EPO分子中与两种受体结合的位点分别位于不同的区域[37]。Leist等[38]将EPO分子中所有赖氨酸通过氨基甲酰化作用转化为瓜氨酸，产生CEPO。体外试验表明CEPO即使在持续高浓度存在的情况下也完全不能与造血细胞上的（EPOR）2结合，且无促红细胞生成的活性，但抑制神经细胞凋亡的活性不变。此外，近来还有研究将EPO与胰岛素样生长因子（IGF1）联合应用[39]，可以产生协同抗凋亡作用，减少给药剂量，减少副作用。另外，在眼局部使用EPO能否降低全身使用EPO所产生的副作用，有待进一步研究证实。
5总结
多种因子相互作用引起视网膜新生血管形成和BRB破坏，是目前研究表明的糖尿病视网膜病变的主要发病机制。在这个机制中起主要作用的因子为VEGF、IGF1、TNFα、IL1β、FGF等。各种研究表明EPO是新的独立的潜在的糖尿病视网膜病变的血管源性因子。而EPO在DR发病中所起的作用，在不同研究中有不同的表现。EPO/EPOR系统对神经系统的营养和神经保护作用已有明确的结论[40]，近年来的实验室研究同样表明EPO/EPOR系统参与了缺血的视网膜神经元的保护。腹腔注射EPO的糖尿病大鼠能够有效地抑制视网膜神经元的损坏。同时也有研究表明EPO/EPOR系统在增殖性糖尿病视网膜病变患者的视网膜新生血管的形成中起着重要的作用。阻断EPO可以抑制玻璃体的新生血管的形成。EPO在糖尿病视网膜病变治疗中的研究尚处于起步阶段，动物试验表明外生性EPO在在早期糖尿病大鼠的玻璃体内注射可防止视网膜细胞的死亡和保护RBR的功能，这可能是对早期DR治疗的一种新的方法。但对晚期的糖尿病视网膜病变的治疗是否可能引起视网膜新生血管的产生，有待进一步的研究。另外，长期大量使用EPO可能产生一些副作用有待进一步的解决。
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