缺氧诱导因子对糖尿病视网膜病变调控作用的研究现状与进展  

Research status and progress of hypoxia-inducible factor on the regulation of diabetic retinopathy

作　　者：贺梦霞 谢洁 孟倩丽[1] He Mengxia;Xie Jie;Meng Qianli(Department of Ophthalmology,Guangdong Provincial People's Hospital,Guangdong Eye Institute,Guangdong Academy of Medical Sciences,Guangzhou 510080,China;School of Medicine,South China University of Technology,Guangzhou 510006,China)

机构地区：[1]广东省人民医院眼科广东省眼病防治研究所广东省医学科学院,广州510080 [2]华南理工大学医学院,广州510006

出　　处：《中华眼底病杂志》2021年第8期661-664,共4页Chinese Journal of Ocular Fundus Diseases

基　　金：广东省自然科学基金(2019A1515010697、2021A1515010921);广州市科技计划项目(202002030400);白求恩·朗沐中青年眼科科研基金(BJ-LM2019004J)。

摘　　要：以血管内皮生长因子(VEGF)为靶点的干预治疗已成为目前治疗糖尿病视网膜病变(DR)的特异性强且有效的方法。但部分患者经抗VEGF药物治疗后无应答或应答不良,并且其消除水肿和改善视力的作用在同一患者中的表现似乎也不稳定。缺氧诱导因子-la(HIF-1a)作为VEGF重要的上游转录调控因子,是组织低氧状态下表达的具有氧浓度敏感性的蛋白,可同时靶向除VEGF之外的诸多下游靶基因,如胎盘生长因子、血管生成素样蛋白4等,引起血视网膜屏障破坏、新生血管形成等,参与DR的多种病理改变,促进DR的发生发展。因此,采用直接干预HIF-1a或靶向一种或多种受HIF-1a调控的下游靶基因治疗DR可能具有更好的疗效。未来研发有效和安全的HIF-1a抑制剂或者抗VEGF协同HIF-1a其他靶基因抑制剂可能具有更广阔的临床应用前景。The intervention therapy targeting vascular endothelial growth factor(VEGF)has become a specific and effective method for the treatment of diabetic retinopathy(DR).However,some patients did not respond or responded poorly to anti-VEGF therapy,and its effects of eliminating edema and improving vision appear to be unstable in the same patient.Hypoxia-inducible factor-la(HIF-la),an important upstream transcriptional regulator of VEGF,is an oxygen concentration-sensitive protein expressed in tissues under hypoxia.It can simultaneously target many downstream target genes except VEGF,such as placental growth factor and angiopoietin-like protein 4,to cause blood-retinal barrier damage and neovascularization,and thus participate in various pathological changes of DR to promote the occurrence and development of DR.Therefore,direct intervention of HIF-la or targeting one or more downstream target genes regulated by HIF-la to treat DR may have better efficacy.In the future,the development of effective and safe HIF inhibitors or anti-VEGF with HIF-la other target gene inhibitors may have broader clinical application prospects.

关 键 词：糖尿病视网膜病变 缺氧诱导因子1 a亚基 血管内皮生长因子类 综述 

分 类 号：R587.2[医药卫生—内分泌] R774.1[医药卫生—内科学]