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格列苯脲调节大鼠低氧高二氧化碳性肺血管收缩时ERK1/2信号的作用

Glybenclamide regulate ERK1/2 signal pathway during hypoxia hypercapnia pulmonary vasoconstriction in rats
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摘要 目的:探究ATP敏感性钾离子通道在低氧高二氧化碳性肺血管收缩(HHPV)中的作用及与细胞外信号调节激酶1/2(ERK1/2)信号通路的关系。方法:制备正常SD大鼠离体三级肺动脉环,建立大鼠离体肺动脉环灌流的模型,用格列本脲(Gly)、Gly+U0126(ERK1/2抑制剂)联合孵育三级肺动脉环,按照低氧高二氧化碳反应性测定方法测定所有血管环的张力值。结果:①常氧状态下,三级肺动脉环的张力值无明显变化;②急性低氧高二氧化碳条件下,三级肺动脉环呈现双向性的收缩(与常氧状态下值相比,P<0.05,P<0.01);③经Gly孵育的三级肺动脉环,其II期收缩幅度增强(与低氧高二氧化碳状态下值相比,P<0.05,P<0.01);④急性低氧高二氧化碳条件下,U0126能使Gly所致的三级肺动脉环II期持续收缩幅度显著降低(与低氧高二氧化碳状态下值相比,P<0.05,P<0.01),I期收缩和I期舒张均没有明显变化(P均>0.05)。结论:ATP敏感性钾离子通道(KATP)阻断剂--Gly可能通过活化ERK1/2信号通路介导了大鼠HHPV的发生。 Objective: To investigate the role and significance of ATP-sensitive K + channels in the pathological process of hypoxia hyper capnia-induced pulmonary vasoconstriction (HHPV) and the relationship with ERK1/2 signal pathway in rats. Methods: We made the third pulmonary artery tings of SD rats, used the model of pulmonary artery tings perfusion in vitro. Under acute hypoxia hypercapnia condition, and observed the effects of the three stages of HHPV incubated by glybenclamide(Gly) and the combined apphcation of Gly and U0126. At the same time, the values of rings' tension changes were recorded v/a the method of hypoxia hypercapnia canditions reactivity. Results: Under the normoxia condition,the values of the third pulmonary artery rings tension were relatively stable, but under the hypoxia hypercapnia condition, we observed a biphasic pulmonary artery contractile response compared with N group( P 〈 0.05, P 〈 0.01). When the third pulmonary artery tings incubated by Gly, it' s phase II persistent vasoconstriction was enhanced compared with the H group ( P 〈 0.05, P 〈 0.01 ), and the phase I vasocomtriction was also heightened. Moreover, under the hypoxia hypereapnia condition, U0126 could significantly relieve the phase Ⅱ persistent vasoconstriction compared with HD group ( P 〈 0.05, P 〈 0.01 ) induced by Gly, but the phase I acute vasoconstriction and the phase I vasodilation had no changes( P 〉 0.05). Condusion: Gly may mediate HHPV v/a activating ERK1/2 signal ttansduetion pathway.
出处 《中国应用生理学杂志》 CAS CSCD 2014年第2期110-114,共5页 Chinese Journal of Applied Physiology
基金 卫生部科学研究基金-浙江省医药卫生重大科技项目(WKJ2009-2-030) 浙江省中医药重点学科建设计划项目(2012-XK-A28)
关键词 低氧高二氧化碳 ATP敏感性钾离子通道 ERK1 2通路 格列本脲 hypoxia hypercapnia ATP-sensitive K + channels ERK1/2 signal pathway glybenclamide
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