School of Medicine and Pharmacology, University of Western Australia, and Stroke Unit, Sir Charles Gairdner Hospital, Perth, WA, Australia.
Clin Sci (Lond). 2011 Dec;121(11):501-7. doi: 10.1042/CS20110215.
CYP450AAM [arachidonic acid metabolites of the CYP450 (cytochrome P450) enzyme system] have a range of biological functions. CYP450AAM are involved in the pathogenesis of hypertension, renal function and vascular function, yet their role in stroke has not been clarified. We aimed at determining the levels of circulating CYP450 metabolites in patients with acute ischaemic stroke (<96 h) compared with healthy age- and gender-matched controls. This was a retrospective case-controlled study of 44 acute ischaemic stroke patients and 44 matched controls. A subset of acute ischaemic stroke patients was available for follow-up. Acute ischaemic stroke patients had elevated plasma CYP450AAM, including 20-HETE (20-hydroxyeicosatetraenoic acid) (1921±170 compared with 1108±170 pmol/l, P<0.001), EETs (epoxyeicosatrienoic acids) (77.88±3.34 compared with 35.35±3.34 nmol/l, P<0.0001) and DiHETEs (dihydroxyeicosatetraenoic acids) (92.87±4.61 compared with 68.17±4.61 nmol/l, P<0.0001), as well as increased plasma F2-isoprostane levels (3754±538 compared with 1947±538 pmol/l, P<0.02), the latter a marker of oxidative stress, compared with controls. In a subset analysis of the stroke patients, plasma 20-HETE, EETs and F2-isoprostanes were attenuated 30 days after the stroke. Baseline 20-HETE levels were also associated with lesion size and functional indices within the stroke patients. The present study highlights the elevation in CYP450AAM and oxidative stress in acute ischaemic stroke patients. Further investigation of the effect this has on long-term clinical outcome or whether this can be modified by treatment is warranted.
CYP450AAM（细胞色素 P450 酶系统的花生四烯酸代谢物）具有多种生物学功能。CYP450AAM 参与高血压、肾功能和血管功能的发病机制，但它们在中风中的作用尚未阐明。我们的目的是确定与健康年龄和性别匹配的对照组相比，急性缺血性中风（<96 小时）患者循环 CYP450 代谢物的水平。这是一项回顾性病例对照研究，共纳入 44 例急性缺血性中风患者和 44 例匹配的对照组。一部分急性缺血性中风患者可进行随访。急性缺血性中风患者的血浆 CYP450AAM 水平升高，包括 20-HETE（20-羟二十碳四烯酸）（1921±170 与 1108±170 pmol/l，P<0.001）、EETs（环氧化二十碳三烯酸）（77.88±3.34 与 35.35±3.34 nmol/l，P<0.0001）和 DiHETEs（二羟二十碳四烯酸）（92.87±4.61 与 68.17±4.61 nmol/l，P<0.0001），以及血浆 F2-异前列烷水平升高（3754±538 与 1947±538 pmol/l，P<0.02），后者是氧化应激的标志物，与对照组相比。在中风患者的亚组分析中，中风后 30 天，血浆 20-HETE、EETs 和 F2-异前列烷水平降低。基线 20-HETE 水平也与中风患者的病灶大小和功能指标相关。本研究强调了急性缺血性中风患者 CYP450AAM 和氧化应激的升高。需要进一步研究这种升高对长期临床结局的影响，或者是否可以通过治疗来改变。
