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。
Objective To observe the effects of ERK1/2 signaling pathway and vascular endothelium cells on 15- KETE-indueed 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. Puhnonary 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 tool/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-intaet 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 1/2 in pulmonary artery smooth muscle cells may also be involved in vasoconstriction induced by 15-KETE in rats.
出处
《实验动物科学》
2013年第6期21-25,共5页
Laboratory Animal Science
基金
黑龙江省应用技术研究与开发计划项目(No.PC13S011)