EPO的组织保护作用临床应用研究进展

Progress of the tissue-protective effect of EPO in clinical trials

促红细胞生成素(EPO),是一种由肾皮质近曲小管周围的间质细胞或基底产生,通过调节和维持循环中红细胞生理水平,提供有效的组织供氧的细胞因子。重组人红细胞生成素(rHuEPO),具有与EPO相同的生物学活性,广泛用于治疗各种原因所致的贫血,减少输血比例,改善预后。在过去的十余年里,EPO的生物多效性被证实,在缺血再灌注、炎症、神经保护、创伤愈合等多种动物模型中被广泛的研究。局部产生的EPO通过与不同于介导红细胞生成的EPO受体结合,激活多条细胞内信号传导通路,减少细胞的程序性死亡,减轻局部炎症反应,发挥组织保护作用。然而,相对于在大量动物实验中的得到的有效结果,EPO在临床实验中的应用却并不让人满意。该文将简要介绍EPO的组织保护作用及机制,讨论其在近期临床试验中的应用和所存在的问题。

Erythropoietin（EPO） is produced in the renal cortex proximal tubule basement membrane or the surrounding stromal cells,which regulates the number of erythrocytes within the circulation to provide adequate tissue oxygenation.Recombinant human erythropoietin（rHuEPO）,which has the same biological activities as the nature EPO,is commonly used in anemia disease.The use of rHuEPO reduce the need for red-cell transfusions and improve the outcomes in some diseases.Over the past 10 years,the pleiotropic effects of EPO have been identified in the animal models including ischaemic-reperfusions injuries,inflammation,neuroprotection,and wound healing.Locally-produced EPO signals through a different receptor isoform and is a major molecular component of the injury response,in which it counteracts the effects of pro-inflammatory cytokines.Although EPO has been demonstrated to be effective in animal models,the effect has not been clearly demonstrated in clinical trials.This review gives a brief introduction to the tissue-protective effect of EPO,and discusses the disappointing results obtained from recent clinical trials.