11月16日,瑞典卡罗林斯卡医学院公布的最新研究成果显示,治疗哮喘的药物具有治疗主动脉瘤的潜能,甚至或可减少患者接受手术治疗的必要。
研究人员在新一期美国《国家科学院学报》上介绍说,主动脉瘤血管壁中的酶含量很高,它促进形成一种名为半胱氨酰白三烯的物质,进而缓慢分解血管壁组织中的蛋白质等多种成分,诱发主动脉瘤。而半胱氨酰白三烯正是引发哮喘的物质,哮喘患者通常都是通过药物来抑制半胱氨酰白三烯的生成来治疗哮喘的。
研究人员因此认为,治疗哮喘的药物有治疗主动脉瘤的潜能。他们将很快着手试验哮喘药物对主动脉瘤的具体疗效。
主动脉瘤是一种高致死性疾病。目前,此病多通过手术治疗,但手术比较复杂并有一定危险。
相关英文论文摘要:
Increased expression of leukotriene C4 synthase and predominant formation of cysteinyl-leukotrienes in human abdominal aortic aneurysm
Leukotrienes (LTs) are arachidonic acid-derived lipid mediators involved in the pathogenesis and progression of diverse inflammatory disorders. The cysteinyl-leukotrienes LTC(4), LTD(4), and LTE(4) are important mediators of asthma, and LTB(4) has recently been implicated in atherosclerosis. Here we report that mRNA levels for the three key enzymes/proteins in the biosynthesis of cysteinyl-leukotrienes, 5-lipoxygenase (5-LO), 5-LO-activating protein (FLAP), and LTC(4) synthase (LTC(4)S), are significantly increased in the wall of human abdominal aortic aneurysms (AAAs). In contrast, mRNA levels of LTA(4) hydrolase, the enzyme responsible for the biosynthesis of LTB(4), are not increased. Immunohistochemical staining of AAA wall revealed focal expression of 5-LO, FLAP, and LTC(4)S proteins in the media and adventitia, localized in areas rich in inflammatory cells, including macrophages, neutrophils, and mast cells. Human AAA wall tissue converts arachidonic acid and the unstable epoxide LTA(4) into significant amounts of cysteinyl-leukotrienes and to a lesser extent LTB(4). Furthermore, challenge of AAA wall tissue with exogenous LTD(4) increases the release of matrix metalloproteinase (MMP) 2 and 9, and selective inhibition of the CysLT1 receptor by montelukast blocks this effect. The increased expression of LTC(4)S, together with the predominant formation of cysteinyl-leukotrienes and effects on MMPs production, suggests a mechanism by which LTs may promote matrix degradation in the AAA wall and identify the components of the cysteinyl-leukotriene pathway as potential targets for prevention and treatment of AAA.
英文论文链接:https://www.pnas.org/content/early/2010/11/08/1015166107