COPD合并慢性缺氧患者肺血管对急性缺氧反应变化中肺动脉平滑肌细胞钾通道的作用

目的：以人离体肺动脉环缺氧张力变化为对象研究钾通道在缺氧性肺血管收缩（HPV）发生中的作用。 方法： 从手术室切取人肺动脉环，进行人肺动脉环张力试验，分正常对照组，单纯慢性阻塞性肺病（chronic obstructive pulmonary disease ，COPD）组和COPD合并慢性缺氧组，分别利用相应的特异性阻断剂观察电压门控性钾通道（KV），钙离子激活的钾通道（KCa）， ATP敏感的钾通道（KATP），在缺氧性肺血管收缩（HPV）的作用。 结果： （1）3组肺动脉环在急性缺氧时血管收缩张力均增加，同时COPD＋慢性缺氧组增加百分比显著低于对照组；COPD组与对照组无显著差异。（2）4-AP阻断Kv后较阻断前，3组肺血管环缺氧张力增加幅度均显著降低（P<0.05），同时正常对照组和COPD组降低幅度明显大于慢性缺氧组。TEA阻断KCa后以及格列苯脲（glybenclamide）阻断KATP后二者较阻断前，3组肺血管环缺氧张力均显著增加（P<0.05），同时COPD＋慢性缺氧组增加的幅度明显大于正常组（分别是P<0.01和P<0.05）。 结论： （1）慢性缺氧可降低肺血管的收缩性及肺血管对急性缺氧的收缩反应；（2）Kv在3组人离体肺动脉环HPV反应中均起介导作用，慢性缺氧可使此介导作用加强；KCa和KATP在3组人离体肺动脉环HPV反应中均起调节作用，慢性缺氧可使此调节作用加强。

Effect of potassium channels on acute hypoxic pulmonary vasoconstriction in COPD and chronic hypoxic patients

AIM: The aim of this study is to investigate the possible role of potassium channel in hypoxic pulmonary vasoconstriction (HPV). METHODS: Fresh human lung tissues were obtained from the Division of Chest Surgery to establish a human model of HPV in vitro. Three groups, control group, COPD group and COPD plus chronic hypoxia group were divided. Human isolated pulmonary artery rings and specific blocking agent corresponding to K_V, K_ Ca, K_ ATP were used to investigate the possible role of the potassium channel in HPV. RESULTS: (1) In acute hypoxia, the vascular ring tension in three groups all increased (P<0.05). Meanwhile, the percentage increase in hypoxic constriction in vascular rings of control group was greater than that in chronic hypoxia group (P<0.05). (2) After inhibition of K_v by 4-AP, in acute hypoxia, the vascular rings tension in three groups all increased (P<0.05), meanwhile, the change range of the vascular ring tension of control gruop was greater than that in chronic hypoxia group (P<0.05). After inhibition of K_ Ca by TEA and inhibition of K_ ATP by glybenclamide, in acute hypoxia, the vascular ring tension of three groups all increased (P<0.05),respectively. Meanwhile, the percentage increase in hypoxic constriction in vascular rings of chronic hypoxia group was greater than that in control group (P<0.01 and P<0.05), respectively. CONCLUSIONS: (1) Chronic hypoxia can blunt human HPV; (2) The closure of K_v channels might mediate HPV in human, chronic hypoxia can reinforce the effect. The opening of K_ Ca channel and K_ ATP channel might modulate HPV in human, and chronic hypoxia may reinforce the effect.