12-脂氧合酶及其代谢产物 12-羟基二十碳四烯酸（12-HETE）在糖尿病视网膜病变中的关键作用。
Key Role of 12-Lipoxygenase and Its Metabolite 12-Hydroxyeicosatetraenoic Acid (12-HETE) in Diabetic Retinopathy.
机构信息
Department of Ophthalmology, Shanghai General Hospital, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Eye Disease Prevention and Treatment Center, Shanghai Eye Hospital, Shanghai, China.
出版信息
Curr Eye Res. 2022 Mar;47(3):329-335. doi: 10.1080/02713683.2021.1995003. Epub 2022 Feb 7.
PURPOSE
Abnormal lipid metabolism has been proved to be implicated in the complex pathogenesis of diabetic retinopathy (DR). 12-lipoxygenase (12-LOX) is a member of lipoxygenase family responsible for the oxygenation of cellular polyunsaturated fatty acids to produce lipid mediators which modulate cell inflammation. This review explores the role of 12-lipoxygenase and its products in the pathogenesis of DR.
METHODS
A comprehensive medical literature search was conducted on PubMed till September 2021.
RESULTS
Emerging evidence has demonstrated that 12-LOX and its main product 12- hydroxyeicosatetraenoic acid (12-HETE) activate retinal cells, especially retinal vascular endothelial cells, through the activation of NADPH oxidase and the subsequent generation of reactive oxygen species (ROS), mediating multiple pathological changes during DR. Genetic deletion or pharmacological inhibition models of 12-LOX in mice show protection from DR.
CONCLUSION
12-LOX and its product 12-HETE take important part in DR pathogenesis and show their potential as future therapeutic targets for DR. Further studies are needed on the specific mechanism including 12-LOX pathway related molecules, 12-HETE receptors and downstream signaling pathways.
目的
异常的脂质代谢被证明与糖尿病视网膜病变（DR）的复杂发病机制有关。12-脂氧合酶（12-LOX）是脂氧合酶家族的一员，负责细胞多不饱和脂肪酸的氧化，产生调节细胞炎症的脂质介质。本综述探讨了 12-脂氧合酶及其产物在 DR 发病机制中的作用。
方法
对 PubMed 上截至 2021 年 9 月的医学文献进行了全面检索。
结果
新出现的证据表明，12-LOX 和其主要产物 12-羟二十碳四烯酸（12-HETE）通过激活 NADPH 氧化酶和随后产生的活性氧（ROS）激活视网膜细胞，特别是视网膜血管内皮细胞，介导 DR 期间的多种病理变化。在小鼠中，12-LOX 的基因缺失或药理学抑制模型显示对 DR 有保护作用。
结论
12-LOX 和其产物 12-HETE 在 DR 的发病机制中起重要作用，并显示出作为 DR 未来治疗靶点的潜力。需要进一步研究具体机制，包括 12-LOX 途径相关分子、12-HETE 受体和下游信号通路。
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