低氧诱导因子在急性肾损伤中作用机制的研究进展

The research progress on the mechanism of hypoxia-inducible factors in acute kidney injury

急性肾损伤(AKI)是由多种病因引起的肾功能快速下降,导致氮代谢(尿素和肌酐)和/或尿量减少而出现的临床综合征,是涉及到临床多学科的问题。AKI的高发病率和死亡率,目前备受临床医生关注。大量实验数据表明低氧诱导因子(hypoxia inducible factor,HIF)的激活可以改善AKI。在低氧/缺血肾脏组织中,HIF在肾小管和肾小球中均有表达。随着对AKI发病机制的研究深入,发现与HIF相关的特殊蛋白、活性化学物质以及基因治疗有望成为AKI治疗的有效手段。通过对于AKI造模动物的研究,提示这些方法通过抑制炎症、氧化应激反应、减少细胞调亡与坏死以及防止肾小管上皮细胞损伤来保护肾脏。本文意在综合论述HIF在AKI中发挥潜在治疗作用的研究进展。

Acute kidney injury(AKI)is a clinical syndrome,which causes rapid decline in renal function for a variety of reasons,and results in decreased nitrogen metabolism(urea and creatinine)and/or decreased urine output.It is involved in clinical multidisciplinary problems.Because of the high morbidity and mortality of acute renal injury,it is the world public health problem that clinicians pay close attention to at present.A large number of experiment data showed that activation of hypoxia inducible factors(HIFs)could improve AKI.HIFs are expressed in both renal tubules and glomeruli in hypoxic/ischemic renal tissues.With the research on the pathogenesis of AKI,the special proteins,active chemicals and gene therapy related to HIF are expected to become effective means of AKI treatment.Studies on AKI model animals suggest that these methods protect the kidney by inhibiting inflammation,oxidative stress response,reducing cell apoptosis and necrosis,and preventing renal tubular epithelial cell injury.The purpose of this article is to summarize the research progress of hypoxia-inducible factor on the potential therapeutic effect on acute kidney injury.