Gobe Glenda C, Morais Christudas, Vesey David A, Johnson David W
Centre for Kidney Disease Research and ; Discipline of Medicine, School of Medicine. The University of Queensland, Brisbane, Australia.
Centre for Kidney Disease Research and ; Department of Nephrology, Princess Alexandra Hospital, Brisbane, Australia.
J Nephropathol. 2013 Jul;2(3):154-65. doi: 10.12860/JNP.2013.27. Epub 2013 Jul 1.
There is a need to define the exact benefits and contraindications of use of high-dose recombinant human erythropoietin (EPO) for its non-hematopoietic function as a cytokine that enhances tissue repair after injury. This review compares the outcomes from use of EPO in the injured heart and kidney, two organs that are thought, traditionally, to have intrinsically-different repair mechanisms.
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Ongoing work by us on EPO protection of ischemia-reperfusion-injured kidneys indicated, first, that EPO acutely enhanced kidney repair via anti-apoptotic, pro-regenerative mechanisms, and second, that EPO may promote chronic fibrosis in the long term. Work by others on the ischaemia-injured heart has also indicated that EPO promotes repair. Although myocardial infarcts are made up mostly of necrotic tissue, many publications state EPO is anti-apoptotic in the heart, as well as promoting healing via cell differentiation and stimulation of granulation tissue. In the case of the heart, promotion of fibrosis may be advantageous where an infarct has destroyed a zone of cardiomyocytes, but if EPO stimulates progressive fibrosis in the heart, this may promote cardiac failure.
A major concern in relation to the use of EPO in a cytoprotective role is its stimulation of long-term inflammation and fibrosis. EPO usage for cytoprotection is undoubtedly advantageous, but it may need to be offset with an anti-inflammatory agent in some organs, like kidney and heart, where progression to chronic fibrosis after acute injury is often recorded.
有必要明确高剂量重组人促红细胞生成素(EPO)作为一种细胞因子在损伤后增强组织修复的非造血功能的确切益处和禁忌证。本综述比较了EPO在受损心脏和肾脏中的应用结果,传统上认为这两个器官具有本质上不同的修复机制。
检索了开放获取期刊目录(DOAJ)、谷歌学术、PubMed(美国国立医学图书馆)、LISTA(EBSCO)和科学引文索引。
我们正在进行的关于EPO对缺血再灌注损伤肾脏保护作用的研究表明,首先,EPO通过抗凋亡、促再生机制急性增强肾脏修复;其次,EPO长期可能促进慢性纤维化。其他人关于缺血性损伤心脏的研究也表明EPO促进修复。尽管心肌梗死主要由坏死组织构成,但许多出版物称EPO在心脏中具有抗凋亡作用,还可通过细胞分化和刺激肉芽组织促进愈合。就心脏而言,在梗死破坏心肌细胞区域的情况下,促进纤维化可能是有利的,但如果EPO刺激心脏进行性纤维化,则可能促进心力衰竭。
EPO用于细胞保护的一个主要问题是其刺激长期炎症和纤维化。EPO用于细胞保护无疑是有益的,但在某些器官,如肾脏和心脏,急性损伤后常进展为慢性纤维化,可能需要用抗炎药来抵消其影响。