缺氧诱导因子1α与核因子κB在炎症缺氧环境中相互作用研究进展

Development on the interaction between hypoxia inducible factor-1αand nuclear factor-κB in inflammatory hypoxic environment

慢性炎症是一系列临床难治疾病(包括心血管损伤、炎性肠病、癌症等)的病理学基础,而缺氧是慢性炎症引起组织损伤的重要病理生理学机制。缺氧诱导因子1α(hypoxia inducible factor-1α,HIF-1α)对组织适应缺氧具有调节作用。缺氧时,HIF-1α通过激活适应性转录反应以协调低氧组织中的氧供应和代谢活性,此过程涉及血管生成因子和血管活性物质等细胞因子的上调。调节免疫应答和细胞凋亡的核因子κB(nuclear factor-κB,NF-κB)具有与HIF-1α类似的功能,即在低氧条件下通过改变氧依赖性脯氨酸羟化酶活性来调节缺氧状态。此文讨论了在多种炎症性疾病中HIF-1α与NF-κB激活通路之间的相互作用,以及HIF-1α和NF-κB通路作为炎症性疾病治疗靶点的潜力。

Chronic inflammation is the pathological basis of a series of refractory diseases,such as cardiovascular injury,inflammatory bowel disease and cancer.Hypoxia is an important pathophysiological mechanism of tissue damage caused by chronic inflammation.Hypoxia inducible factor-1α(HIF-1α)can regulate tissue adaptation to hypoxia.During hypoxia,HIF-1αcoordinates oxygen supply and metabolic activity in hypoxic tissues by activating adaptive transcriptional responses,which involve the up-regulation of cytokines such as angiogenic factors and vasoactive substances.Nuclear factor-κB(NF-κB),the key factor regulating immune response and apoptosis,has a similar function to HIF-1α,i.e.,regulating hypoxia by changing the activity of oxygen-dependent proline hydroxylase under hypoxic conditions.This review discusses the interaction between HIF-1αand NF-κB activation pathways in a variety of chronic inflammatory diseases and the potential of both HIF-1αand NF-κB activation pathways as therapeutic targets for inflammatory diseases.