MAPK 通路抑制剂对低氧高二氧化碳性肺动脉收缩的影响

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、p38 MAPK 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 = 30-35 mmHg，PCO₂=55-60 mmHg)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。

Effect of MAPK inhibition on the hypoxia hypercapnia-induced pulmonary vasoconstriction

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 hypercapnia 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 hypercapnia 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 hypercapnia in the second pulmonary artery rings 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 hypercapnia 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.