Gassmann Max, Heinicke Katja, Soliz Jorge, Ogunshola Omolara O
Institute of Veterinary Physiology, University of Zürich, Switzerland.
Adv Exp Med Biol. 2003;543:323-30. doi: 10.1007/978-1-4419-8997-0_22.
The oxygen-dependent, renal cytokine eythropoietin (Epo) is well known to increase red cell production. Binding of Epo to the Epo receptor (EpoR) represses apoptosis of erythroid progenitor cells, thereby allowing their final maturation. We and others showed that Epo and its receptor are expressed in many other tissues, including brain, spinal cord, retina and testis. The presence of a blood barrier suggests that Epo plays a local role in these organs. Indeed, therapeutically applied or hypoxically induced Epo has been shown to reduce the infarct volume in various stroke animal models, to prevent retinal degeneration, and to ameliorate spinal cord injury. In a study conducted by Ehrenreich and colleagues, stroke patients treated with Epo showed reduced infarct volume, fast neurological recovery and improved clinical outcome. In analogy to its function on erythroid progenitor cells, this neuroprotective effect of Epo might be explained by repression of programmed cell death. Apart from neuroprotection, there is an assumption that Epo present in breast milk has the potential to protect against mother-to-infant transmission of HIV. When using Epo at high doses for longer time periods; however, care has to be taken to control the resulting chronic polycythemia that most probably caused enlarged cerebral infarct volumes in a transgenic mouse model that due to Epo-overexpression reached hematocrit levels of about 0.8. Overall, these data strongly support the notion that Epo will soon find new applications in the clinic.
氧依赖性的肾脏细胞因子促红细胞生成素（Epo）以增加红细胞生成而闻名。Epo与促红细胞生成素受体（EpoR）结合可抑制红系祖细胞的凋亡，从而使其最终成熟。我们和其他人的研究表明，Epo及其受体在包括脑、脊髓、视网膜和睾丸在内的许多其他组织中表达。血脑屏障的存在表明Epo在这些器官中发挥局部作用。事实上，治疗性应用或低氧诱导的Epo已被证明可减少各种中风动物模型中的梗死体积，预防视网膜变性，并改善脊髓损伤。在Ehrenreich及其同事进行的一项研究中，接受Epo治疗的中风患者梗死体积减小，神经功能恢复加快，临床结局改善。与其对红系祖细胞的作用类似，Epo的这种神经保护作用可能是通过抑制程序性细胞死亡来解释的。除了神经保护作用外，有一种假设认为母乳中的Epo有可能预防母婴间的HIV传播。然而，当长时间高剂量使用Epo时，必须注意控制由此产生的慢性红细胞增多症，在一个转基因小鼠模型中，由于Epo过表达导致血细胞比容达到约0.8的水平，这种慢性红细胞增多症很可能导致脑梗死体积增大。总体而言，这些数据有力地支持了Epo很快将在临床上找到新应用的观点。
