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MAPK通路抑制剂对低氧高二氧化碳性肺动脉收缩的影响 被引量:16

Effect of MAPK inhibition on the hypoxia hypercapnia-induced pulmonary vasoconstriction
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摘要 目的:观察肺主动脉环、二级肺动脉环在急性低氧高二氧化碳介质中张力的变化;探讨MAPK信号通路抑制剂U0126、SB203580对低氧高二氧化碳性肺血管收缩的影响。方法:制备离体SD大鼠肺主动脉环、二级肺动脉环。分别观察肺主动脉环、二级肺动脉环在常氧及急性低氧高二氧化碳介质中的张力变化;在急性低氧高二氧化碳条件下分别用U0126、SB203580孵育二级肺动脉,观察各自对低氧高二氧化碳性肺动脉收缩的影响。结果:在常氧条件下,肺主动脉、二级肺动脉张力均无明显变化。急性低氧高二氧化碳条件下二级肺动脉发生双向性收缩反应,肺主动脉只在低氧高二氧化碳早期出现较明显的收缩峰,后期则变化不明显。二级肺动脉分别经ERK1/2上游激酶抑制剂U0126、p38MAPK通路抑制剂SB203580孵育后,Ⅱ期持续收缩幅度明显下降(P<0.05),Ⅰ期快速收缩峰、Ⅰ期舒张均没有明显变化。结论:在离体条件下,急性低氧高二氧化碳(PO2=30-35mmHg,PCO2=55-60mmHg)可使肺主动脉出现早期快速收缩,并可使二级肺动脉环发生双向性收缩反应;急性低氧高二氧化碳条件下,U0126、SB203580均能减弱二级肺动脉环的Ⅱ期持续收缩反应。这为临床治疗缺氧和高碳酸血症引起的肺血管收缩及肺动脉高压提供了理论依据。 AIM: To investigate isometric force displacement in isolated rat main pulmonary artery rings and right main branch pulmonary artery (second pulmonary artery) rings during hypoxia hypereapnia and the role of mitogen activated protein kinase (MAPK). METHODS: The main pulmonary artery rings were dissected from the male Sprague - Dawley rats and were randomly divided into control group and hypoxia hypercapnia group. The second pulmonary artery rings were also randomly divided into control group, hypoxia hypereapnia group, DMSO incubation group, U0126 incubation group and SB203580 incubation group. The tension changes of pulmonary artery rings were monitored in vitro. RESULTS: Under normoxia conditions, there was no statistically significant change between main pulmonary artery rings and second pulmonary artery rings. A biphasic pulmonary artery contractile response to hypoxia hypereapnia in the second pulmonary artery tings was observed instead of a sharp and transient increase in the main pulmonary artery tension. Both p38 MAPK inhibitor SB203580 and ERK1/2 inhibitor U0126 significantly attenuated the delayed, but not early, contractile phase of the biphasic pulmonary artery contraction. CONCLUSION : Acute hypoxia hypereapnia causes a biphasic pulmonary artery contractile response in the second pulmonary artery, and p38 MAPK and ERK1/2 may be two key mediators in the process.
出处 《中国病理生理杂志》 CAS CSCD 北大核心 2008年第8期1538-1542,共5页 Chinese Journal of Pathophysiology
基金 浙江省科技攻关资助项目(No.2006C33073)
关键词 肺动脉 低氧 高碳酸血 细胞外信号调节激酶类 p38 MAP激酶 Pulmonary artery Hypoxia Hypercapnia Extracellular signal -regulated kinases p38 MAP kinase
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参考文献16

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