实验动物科学 ›› 2013, Vol. 30 ›› Issue (06): 21-25.

• 研究 论著 • 上一篇    下一篇

ERK1 /2 通路和血管内皮细胞在15-KETE 诱导缺氧大鼠 肺动脉收缩中的作用*

  

  1. (1. 哈尔滨医科大学第二临床医学院实验动物中心,哈尔滨150086)
    (2. 哈尔滨医科大学第二临床医学院药学部,哈尔滨150086)
    (3. 哈尔滨医科大学公共卫生学院职业卫生与职业医学教研室,哈尔滨150086)
  • 出版日期:2013-12-31 发布日期:2014-05-15
  • 基金资助:

    黑龙江省应用技术研究与开发计划项目(No. PC13S011)

Effect of ERK1 /2 Signaling Pathway and Vascular Endothelium Cells on Pulmonary Artery Constriction in Chronic Hypoxic Rats Induced by 15-KETE

  • Online:2013-12-31 Published:2014-05-15

摘要: 摘要:目的用组织浴槽血管环技术研究细胞外信号调节激酶1 /2( extracellular regulated protein kinases1 /2,ERK1 / 2)通路和血管内皮细胞在15-KETE 诱导缺氧大鼠肺动脉收缩中的作用。方法16 只体质量为(220 ± 20) g 清洁级 Wistar 大鼠随机分为2 组( n = 8),正常对照组置于正常环境中饲养( FiO2 = 21% ),缺氧组置于缺氧的培养箱中饲 养( FiO2 = 10% ),连续饲养9 d 后处死,游离直径约为0. 5—1. 0 mm 肺内肺动脉( PA)。剪成3 mm 长的动脉环,在 组织浴槽内进行张力研究。比较在15-KETE 给药前后肺动脉环张力变化;机械法去除动脉环内皮,比较内皮完整 和去内皮后,15-KETE 对缺氧性肺动脉环的收缩作用;用ERK1 /2 上游激酶抑制剂U0126 孵育肺动脉环,比较 U0126 孵育前后15-KETE 对缺氧性肺动脉环的收缩作用;机械法去除动脉环内皮,再比较U0126 孵育前后15- KETE 对缺氧性肺动脉环的收缩作用。结果1) 15-KETE 对缺氧大鼠肺动脉环有收缩作用,呈浓度一效应关系, 与正常对照组比较差异显著(P < 0. 05) ;2) 内皮完整和内皮去除的肺动脉环,15-KETE 对其缩血管作用均受到抑 制,但差异显著(P < 0. 05) ;3) 内皮完整肺动脉环,在U0126 孵育前后,15-KETE 的缩血管作用均受到抑制,但差异 显著(P < 0. 05) ;4)内皮去除的肺动脉环,U0126 孵育前后,15-KETE 的缩血管作用也受到抑制,差异显著( P < 0. 05)。结论15-KETE 可浓度依赖性地收缩缺氧大鼠肺动脉环;15-KETE 引起缺氧肺动脉收缩可能与ERK1 /2 信 号转导通路和血管内皮细胞有关,并且位于平滑肌的ERK1 /2 通路也参与15-KETE 诱导缺氧大鼠肺动脉环的 收缩。

关键词: 15-KETE, 肺动脉环, 缺氧, 细胞外信号调节激酶, 肺动脉血管内皮细胞

Abstract: Abstract:Objective To observe the effects of ERK1 /2 signaling pathway and vascular endothelium cells on 15- KETE-induced chronic hypoxic pulmonary artery constriction in rats using organ bath technique. Method Sixteen healthy Wistar rats (220 ± 20) g were randomly divided into two groups ( n = 8 each group) : normoxia and hypoxia groups housed in fresh air ( FiO2 = 21% ) and hypoxic air ( FiO2 = 10% ) in a hypoxic box,respectively. Pulmonary arteries( PA) were extracted after 9 days and cut into rings ( 0. 5 ~ 1. 0mm in diameter and 3mm in length) for organ bath experiments. The ring tensions before and after 15-KETE induction were compared. Influences of ERK1 /2 upstream kinase inhibitor U0126 and endothelium integrity on 15-KETE induced HPV were investigated. Result With concentration increasing from 0 to 10 - 6 mol /L,15-KETE increased PA rings tension gradually in a dose-dependent fashion,and significantly constricted PA rings from the hypoxic rats. Response of the hypoxic rings were significantly greater than that of normoxic ones (P < 0. 05) . The ring tensions induced by 15- KETE in endothelium-intact PAs were significantly greater than that in endothelium-denuded ones ( P < 0. 05 ) . U0126 significantly reduced vasoconstriction induced by 15-KETE in both endothelium-intact and -denuded rings. ( P < 0. 05 in both) . Conclusion 15-KETE significantly constricted PA rings in hypoxic rats in a dose-dependent fashion; ERK1 /2 signaling pathway and vascular endothelium cells may be involved in vasoconstriction induced by 15-KETE,and ERK l /2 in pulmonary artery smooth muscle cells may also be involved in vasoconstriction induced by 15-KETE in rats.

Key words: 15-KETE, pulmonary artery ring, hypoxia, ERK1 /2, endothelium cells of pulmonary artery

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