5-脂氧合酶及其相关产物与心脑血管损伤的研究进展  

Advances in study on role of 5-lipoxygenase and its relevant products in cardio-cerebrovascular injury

作　　者：黄林露 彭军 HUANG Lin-lu;PENG Jun(Dept of Pharmacology,Xiangya School of Pharmaceutical Sciences,Central South University,Changsha 410013,China)

机构地区：[1]中南大学湘雅药学院药理学系,湖南长沙410013

出　　处：《中国药理学通报》2025年第1期13-18,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 82173815,81872873)。

摘　　要：5-脂氧合酶(5-lipoxygenase,5-LOX)是生成重要炎性介质白三烯和促炎症消退介质的关键酶。既往研究表明,5-LOX的异常激活和白三烯的过量产生与心肌缺血/再灌注损伤、缺血性脑损伤和动脉粥样硬化等损伤相关性心脑血管疾病的发生与发展密切相关。靶向抑制5-LOX及其相关产物级联反应中的酶和受体能够对心脑血管损伤起到保护作用,表明5-LOX及其相关产物可能是治疗心脑血管疾病潜在的靶点。已有的相关抑制剂包括5-LOX/5-LOX激活蛋白抑制剂、白三烯A4水解酶/白三烯C4合成酶抑制剂、白三烯受体拮抗剂,这些抑制剂通过不同的机制减轻炎症,抑制促炎介质白三烯的产生,促进抗炎脂质介质的形成,在心肌缺血/再灌注损伤和动脉粥样硬化的治疗中显示出了潜在的价值。该文综述了5-LOX及其相关产物在心脑血管疾病中的作用,同时总结了相关抑制剂在心脑血管应用中的研究进展。5-lipoxygenase(5-LOX)is a key enzyme in producing important inflammatory mediator leukotrienes and pro-resolving lipid mediators.Previous studies have shown that abnormal activation of 5-LOX and excessive production of leukotrienes play an important role in the progression of injury-related cardio-cerebrovascular disorders such as myocardial ischemia/reperfusion injury,ischemic brain injury and atherosclerosis.Targeted inhibition of enzymes and receptors in the pathway of 5-LOX and its relevant products can exert a protective effect on cardio-cerebrovascular injury,indicating that 5-LOX and its relevant products may be a potential target for the treatment of cardio-cerebrovascular disorders.Existing related inhibitors include 5-LOX/5-LOX activating protein inhibitors,leukotriene A4 hydrolase/leukotriene C4 synthase inhibitors,and leukotriene receptor antagonists.These inhibitors alleviate inflammation through different mechanisms,inhibiting the production of pro-inflammatory mediator leukotrienes,promoting the formation of pro-resolving lipid mediators,which possess potential value in the treatment of myocardial ischemia/reperfusion injury and atherosclerosis.This review focuses on the role of 5-LOX and its relevant products in cardio-cerebrovascular diseases,and summarizes studies on the efficacy of related inhibitors in treating cardio-cerebrovascular disorders.

关 键 词：5-脂氧合酶 心肌缺血/再灌注 心肌梗死 缺血性脑损伤 动脉粥样硬化 5-脂氧合酶抑制剂 

分 类 号：R363[医药卫生—病理学]