ERK1／2通路参与15-羟二十碳四烯酸收缩缺氧大鼠肺动脉的过程(英文)  

ERK1/2 signaling pathway is involved in 15-hydroxyeicosatetraenoic acid-induced hypoxic pulmonary vosoconstriction

作　　者：吕昌莲[1] 叶宏[1] 唐晓波[1] 朱大岭[1] 

机构地区：[1]哈尔滨医科大学药学院

出　　处：《生理学报》2005年第5期605-611,共7页Acta Physiologica Sinica

基　　金：This work was supported by the National Natural Science Foundation of China(No.30370578),ScienceTechnology Foundation of Educational Office of Heilongjiang Province(No.10551174)Graduate Innovation Foundation of Harbin Medical University.

摘　　要：缺氧诱导的15-羟二十碳四烯酸(15-hydroxyeicosateteraenoic acid,15-HETE)是引起肺动脉收缩的重要介导因子。15- HETE引起肺动脉收缩的信号转导途径尚不清楚。本研究旨在确定细咆外信号调节激酶1／2(extracellular signal-regulated kinase-1／2, ERK1／2)信号转导通路是否参与15-HETE收缩缺氧大鼠肺动脉的过程。采用组织浴槽肺动脉环张力检测、蛋白质免疫印迹 (Western blot)和免疫细胞化学方法。制备缺氧大鼠动物模型,成年雄性Wistar大鼠在低氧环境下(吸入氧分数为0．12)正常喂养 9 d。显微分离直径1～1．5mm肺动脉,剪成长为3 mm的动脉环,进行血管张力检测。用ERK1／2 上游激酶(MEK)抑制剂PD98059 抑制ERK1／2活性。结果显示,PD98059可明显抑制15-HETE对缺氧大鼠肺动脉环的收缩作用。在去除内皮的肺动脉环, PD98059仍可明显降低15-HETE的缩血管作用。Western blot和免疫细胞化学结果都显示,15-HETE能促进ERK1／2磷酸化。 由此表明ERK1/2信号转导通路参与15-HETE收缩缺氧大鼠肺动脉的过程。Hypoxia-induced 15-hydroxyeicosatetraenoic acid （15-HETE） is an essential mediator to constrict pulmonary arteries （PA）. The signaling pathway involved in 15-HETE-induced PA vasoconstriction remains obscure. The aim of the present study was to test the hypothesis that hypoxic PA constriction induced by 15-HETE was possibly regulated by the extracellular signal-regulated kinase-1/2 （ERK1/2） pathway. PA ring tension measurement, Western blot and immunocytochemistry were used in the study to determine the possible role of ERK1/2 in 15-HETE-induced PA vasoconstriction. The organ bath for PA rings tension study was employed. Adult male Wistar rats were raised in hypoxic environment with fractional inspired oxygen （FIO2, 0.12） for 9 d. PA 1-1.5 mm in diameter were dissected and cut into 3 mm long rings for tension study. ERK1/2 up-stream kinase （MEK） inhibitor PD98059, which blocks the activation of ERK1/2, was used. The results showed that pretreatment of PD98059 significantly blunted 15-HETE-induced PA vasoconstrictions in the rings from hypoxic rat. Moreover, in endothelium-denuded rings, PD98059 also significantly attenuated 15-HETE-induced vasoconstriction. Phosphorylation of ERK1/2 in pulmonary arterial smooth muscle cells （PASMCs） of rat was enhanced evidently when stimulated by 15-HETE. Thus, the data suggest that ERK1/2 signaling pathway is involved in 15-HETE- induced hypoxic pulmonary vasoconstriction.

关 键 词：缺氧 15-羟二十碳四烯酸 15-脂氧化酶 细胞外信号调节激酶 

分 类 号：R33[医药卫生—人体生理学]