低氧诱导因子通路在心肾综合征中的作用及低氧诱导因子稳定剂的应用前景

Role of hypoxia inducible factor pathway in cardiorenal syndrome and application prospect of HIF stabilizer

心肾综合征(cardiorenal syndrome,CRS)是一种多器官疾病,是指心脏或肾脏其中之一的急性或慢性功能障碍引起另一器官的急性或慢性功能障碍,其病理生理涉及免疫炎症、氧化损伤、贫血、铁代谢紊乱、血脂异常、血流动力学障碍、内皮功能障碍、神经激素等多个方面。缺氧是心肾疾病发生发展常见的诱因,人体在缺氧条件下低氧诱导因子(hypoxia-inducible factor,HIF)表达上调,HIF通过多个途径调节各种靶基因的转录,对炎症、氧化应激、脂质代谢等CRS的发病机制产生影响,因而有可能成为治疗CRS的一个潜在靶点。HIF脯氨酰羟化酶抑制剂作为HIF稳定剂可抑制HIF降解,故可能具有潜在的心肾保护作用。在此,我们对HIF在CRS中的作用机制进行综述,以期更好地了解二者之间的联系,并探讨HIF稳定剂在CRS中的应用前景。

Cardiorenal syndrome(CRS)involves multiple organs.It refers to acute or chronic cardiac or renal dysfunction.Its pathophysiology involves immune inflammation,oxidative damage,anemia,iron metabolism disorders,dyslipidemia,hemodynamic disorders,endothelial dysfunction and neurohormonal mechanisms.Hypoxia is a common induced for the occurrence and development of cardiac or renal diseases.Up-regulated under hypoxia,hypoxia inducible factor(HIF)regulates the transcription of various target genes through multiple pathways and affects the pathogenesis of cardiorenal syndrome,such as inflammation,oxidative stress and lipid metabolism.Therefore HIF may become a potential therapeutic target for CRS.As a HIF stabilizer,HIF prolyl hydroxylase inhibitor can suppress the degradation of HIF so as to offer potential cardio-protective and renal-protective effects.Here the mechanism of HIF was reviewed for better understanding their links and exploring the application prospects of HIF stabilizerin CRS.