白三烯与动脉粥样硬化

炎症反应促进粥样斑块进展和不稳定斑块的形成与破裂,导致心脑血管事件发生。白三烯(LTs)作为一类炎症介质来参与动脉粥样硬化(AS)日益受到重视。积极寻找和应用阻断LTs通路的药物以防治AS,成为新的研究热点。本文就LTs在AS中的作用和临床应用进展作一综述。     

白三烯与动脉粥样硬化

炎症反应促进粥样斑块进展和不稳定斑块的形成与破裂,导致心脑血管事件发生。白三烯（LTs）作为一类炎症介质来参与动脉粥样硬化（AS）日益受到重视。积极寻找和应用阻断LTs通路的药物以防治AS,成为新的研究热点。本文就LTs在AS中的作用和临床应用进展作一综述。     

白三烯与动脉粥样硬化的研究进展

炎症反应是动脉粥样硬化的主要致病机制,白三烯是参与炎症反应的一种重要炎性介质。本文综述了白三烯及其代谢途径中的相关物质参与动脉粥样硬化的发病机制,以及抗白三烯药物治疗动脉粥样硬化的作用。     

白三烯在动脉粥样硬化形成中的作用

<正>白三烯(LT)作为体内重要的炎性介质,已发现与哮喘发病密切相关。近年来动物和人体实验结果表明LT在动脉粥样硬化(AS)发生中发挥重要作用,主要包括增强炎性细胞黏附血管壁细胞,增加血管通透性,降解细胞外基质(ECM)、加剧血管炎性反应等多方面作用〔1〕。1 LT物特性LT是一种由脂质衍生的炎性介质,花生四烯酸在5-脂氧合酶(LOX)、5脂氧合酶激活蛋白(FLAP)作用下生成不稳定环     

白三烯与支气管哮喘

哮喘是一种以可逆性气道阻塞和非特异性气道高反应性为特征的慢性炎症疾病,涉及一系列炎性细胞和炎性介质的复杂过程.白三烯（leukotrienes,LTs）是花生四烯酸经5-脂氧酶途径合成代谢的一系列产物,是哮喘发病机制中重要的炎症介质之一.     

白三烯与支气管哮喘

哮喘是一种以可逆性气道阻塞和非特异性气道高反应性为特征的慢性炎症疾病,涉及一系列炎性细胞和炎性介质的复杂过程。白三烯(leukotrienes,LTs)是花生四烯酸经5-脂氧酶途径合成代谢的一系列产物,是哮喘发病机制中重要的炎症介质之一。1LTs的生物合成细胞(主要是炎症细胞)在刺激因素的作用下被激活,细胞膜磷脂被磷脂酶A2(PLA2)裂解为花生四烯酸(AA),AA结合到5-脂氧酶激活蛋白(FLAP),再递呈给转移到核膜上的5-LO,被5-LO氧化为5-羟过氧化二十碳四烯酸(5-HPETE),然后再5-LO作用下进一步氧化为不稳定的环化物白三烯A4(LTA4)。LTA4…     

白三烯与肺部疾病

在20碳脂肪酸的代谢产物中,AA 是平滑肌张力和组织炎症的强力介质,虽每种体液和组织中均有 AA,但肺受其影响最为主要.已证实 LT 与许多疾病密切相关.本文综述 LT 与肺部一些疾病的关系,以及 LT 的抑制剂之研究若干近况.LT 的形成LT 来源于白细胞,且含三烯分子结构。LT 的形成:5-羟过氧化花生四烯酸(HPETEs)经谷胱甘肽过氧化酶系转化成相应的单羟基脂肪酸或不稳定的中间物 LTA_4,LTA_4经水解酶的作用可变成成 LTB_4,LTP_4通过白细胞代谢生成比 LTB_4活性     

白三烯与阿斯匹林哮喘

随着发现阿斯匹林哮喘(aspirin sensitive asthma,ASA)与环氧化酶(cycloxygenase,COS)及5-脂氧化酶(5-lipoxygenase,5-LO)途径介导有关,近年对白三烯(LT)在ASA发病过程中的认识已取得了重大进展,已知ASA者于摄入阿斯匹林后,来源于嗜酸粒细胞和肥大细胞的LT分泌亢进,尤其在肺部。LT作为效应介质,其效应产生与抗COX活性有关。应用抗LT和抗5-LO拮抗剂能通过降低受体对LET_4的敏感性和(或)减少LT的生成而改善或控制ASA的症状。现就ASA的发病及治疗有关方面对白三烯的认识及研究动向和进展作一综述。     

白三烯与脑血管疾病

近年来,大量实验表明,白三烯类(LTs)与脑血管疾病的病理生理过程具有非常密切的关系。本文就 LTs 的生物合成,生物学活力,作为介质的功能,及其拮抗物的应用进行了讨论。     

Leukotriene antagonists

Hepatotoxicity is the most common cause of fulminant hepatic failure in the United States and the main indication for market withdrawal of drugs. This condition has been increasingly recognized as a problem of enormous medical, financial legal, and regulatory importance. It is in context of this heightened awareness of hepatotoxicity, particularly associated with new high profile drugs, that the authors reviews the published data regarding liver injury related to a novel group of asthma drugs.     

Leukotriene B4 signaling through NF-kappaB-dependent BLT1 receptors on vascular smooth muscle cells in atherosclerosis and intimal hyperplasia

Leukotriene B(4) (LTB(4)), a potent leukocyte chemoattractant derived from the 5-lipoxygenase metabolism of arachidonic acid, exerts its action by means of specific cell surface receptors, denoted BLT(1) and BLT(2). In this study, BLT(1) receptor proteins were detected in human carotid artery atherosclerotic plaques, colocalizing with markers for macrophages, endothelial cells, and vascular smooth muscle cells (SMC). Challenge of human coronary artery SMC with either LTB(4) or U75302, a partial agonist that is selective for the BLT(1) receptor, induced an approximately 4-fold increase of whole-cell currents by using the patch-clamp technique, indicating that these cells express functional BLT(1) receptors. LTB(4) induced migration and proliferation of SMC in vitro, and treatment with the BLT receptor antagonist BIIL 284 (10 mg/kg, once daily) for 14 days after carotid artery balloon injury in vivo inhibited intimal hyperplasia in rats. In the latter model, SMC derived from the intima exhibited increased levels of BLT(1) receptor mRNA compared with medial SMC. BLT receptor up-regulation in the intima in vivo, as well as that induced by IL-1beta in vitro, were prevented by transfection with a dominant-negative form of Ikappa kinase beta carried by adenovirus, indicating that BLT(1) receptor expression depends on NF-kappaBeta. These results show that LTB(4) activates functional BLT(1) receptors on vascular SMC, inducing chemotaxis and proliferation, and that BLT(1) receptors were up-regulated through an Ikappa kinase beta/NF-kappaB-dependent pathway. Inhibition of LTB(4)/BLT(1) signaling during the response to vascular injury reduced intimal hyperplasia, suggesting this pathway as a possible target for therapy.     

Leukotriene receptor antagonists

In the past decade, heightened emphasis has been placed on the importance of inflammation in the pathogenesis of asthma. Although corticosteroids have remained the primary anti-inflammatory agents in the management of the persistent asthmatic, new classes of drugs have recently been added. The leukotriene receptor antagonists (LTRAs) are the first new approach in asthma therapy in the past 25 years and the first class of drugs to target specific components of the inflammatory process. These drugs reverse the primary biological effects of the cysteinyl leukotrienes in relation to the pathogenesis of asthma including bronchoconstriction, mucus hypersecretion, and airway inflammation. The LTRAs have demonstrated efficacy against exercise- and allergen-induced bronchoconstriction, aspirin-sensitive asthma, and additive benefit in symptomatic moderate asthmatics on maintenance inhaled corticosteroids, as well as potential steroid-sparing effects. Finally, although evidence for their role as first-line controller agents for the management of mild persistent asthma has grown stronger in recent years, this role continues to evolve.     

咳嗽变异性哮喘与白三烯关系的研究进展

咳嗽变异性哮喘（CVA）是以咳嗽为唯一或主要临床表现的特殊类型的哮喘,其发病机制及病理生理与典型哮喘相似,两者均以持续气道炎症、气道高反应性和气道重构为特点,平均约有30％的CVA患儿最终发展为典型哮喘。白三烯（LTs）是体内重要的炎症介质,LTs及其拮抗剂在CVA的发病和治疗中起重要作用。在CVA的治疗对策中,早期干预具有重要临床意义,在众多合理、有效的指导与治疗选项中,LTs拮抗剂不失为一项有效、安全的选择。该文就CVA与LTs关系的研究进展作一综述。     

Leukotriene receptors in rhinitis and sinusitis

Cysteinyl leukotrienes (CysLTs) mediate their biologic activities through interactions with the CysLT1 and CysLT2 receptors. CysLT1 receptors are prominently expressed on smooth muscle cells and lung fibroblasts, whereas CysLT2 receptors are expressed on heart Purkinje fiber cells, adrenal chromaffin cells, and endothelial cells. Both receptors are expressed on eosinophils and mast cells, but CysLT1 receptors alone are on neutrophils. Antigen-presenting cells more prominently express the type 2 receptor. CysLT1 receptors are uniquely important for brochospasm, whereas CysLT2 receptors can stimulate endothelial cell adherence, myofibroblast proliferation, and chemokine production by mast cells. Comprehensive inhibition of the proinflammatory activities of CysLTs might require either combination CysLT1 and CysLT2 receptor antagonists or inhibitors of the CysLT synthesis pathway.     

Leukotriene Signaling in Atherosclerosis and Ischemia

Introduction  The inflammatory process of atherosclerosis is associated with several pathophysiological reactions within the vascular wall. The arachidonic acid released by phospholipase A₂ serves as substrate for the production of a group of lipid mediators known as the leukotrienes, which induce pro-inflammatory signaling through activation of specific BLT and CysLT receptors. Discussion  Leukotriene signaling has been implicated in early lipid retention and foam cell accumulation, as well as in the development of intimal hyperplasia and advanced atherosclerotic lesions. Furthermore, the association of leukotrienes with degradation of extracellular matrix has suggested a role in atherosclerotic plaque rupture. Finally, studies of either myocardial or cerebral ischemia and reperfusion indicate that leukotriene signaling in addition may be involved in the development of ischemic injury. Conclusion  Both leukotriene synthesis inhibitors and leukotriene receptor antagonists have been suggested to induce beneficial effects at different stages of the atherosclerosis process.     

Leukotriene generation and clinical implications.

Since the elucidation of the structure of the cysteinyl leukotrienes (LTs) > 20 years ago, considerable progress has been made in our understanding of the role of these molecules in health and disease, particularly regarding bronchial asthma. This study will review the biochemistry of the 5-lipoxygenase pathway for LT generation. It will discuss the early evidence that LTs, the cysteinyl LTs in particular, have the biological properties expected for molecules that participate in the pathogenesis of bronchial asthma and the evidence for their formation in the airways of asthmatic individuals. It will briefly review tile evidence that LT-modifying drugs are effective in the management of bronchial asthma and will discuss novel developments in our understanding of the proinflammatory properties of the LTs including their role as autocrine mediators of leukocyte responses. The pharmacogenomics of 5-lipoxgenase and LTC4 synthase in bronchial asthma will be discussed.