HIF脯氨酰羟化酶抑制剂治疗肾性贫血的临床研究进展

Clinical advances in renal anemia treatment with HIF prolyl hydroxylase inhibitors

缺氧诱导因子(HIF)是细胞低氧反应的关键转录因子,负责调控包括促红细胞生成素(EPO)在内的多种缺氧相关基因的转录,对缓解疾病具有重要作用。脯氨酰羟化酶(PHD)是HIF降解反应的限速酶。PHD抑制剂能有效稳定HIF,增加HIF的含量,从而达到治疗的目的。本文综述了目前临床上用于治疗肾性贫血的PHD抑制剂的研究进展,以及部分抑制剂的作用机制。

Hypoxia inducible factor（ HIF） is the key transcriptional factor of cellular response to hypoxia, regulating the hypoxia related genes transcription, such as erythropoietin（EPO）, and plays a criticalrole in hypoxia related diseases. Prolyl hydroxylase（PHD） is the speed limiting enzyme of HIF degradation. The PHD inhibitors can effectively stabilize HIF and increase the quantity of HIF, so as to achieve the purpose of treatment. In this short review, the recent progress of PHD inhibitors currently in clinical trials for renal anemia treatment were introduced, and the mechanisms of inhibition of some PHD inhibitors were described.