慢性缺氧抑制肺动脉平滑肌细胞钾通道活性  

Inhibition of potassium channel by chronic hypoxia on pulmonary artery smooth muscle cells in rats

作　　者：肖欣荣[1] 陈文彬[1] 程德云[1] 

机构地区：[1]华西医科大学附属第一医院呼吸内科

出　　处：《中华结核和呼吸杂志》1998年第11期681-685,共5页Chinese Journal of Tuberculosis and Respiratory Diseases

基　　金：国家"九五"科技攻关;国家自然科学基金

摘　　要：目的研究慢性缺氧性肺动脉高压发生机制中钾通道活性改变的作用，及其开放剂卡吗克林（ｃｒｏｍａｋａｌｉｍ）对钾通道活性的调控作用。方法２０只Ｗｉｓｔａｒ大鼠随机分为对照组１０只和缺氧组１０只，缺氧组大鼠缺氧３周，每天缺氧８小时；运用急性酶分离法对Ｗｉｓｔａｔ大鼠肺动脉平滑肌细胞进行了分离；应用膜片钳小片膜单通道技术，分别对正常和慢性缺氧３周大鼠的肺动脉平滑肌细胞的钾离子通道进行了测定；记录并比较了两组大鼠肺动脉平滑肌细胞钙、ＡＴＰ激活性钾通道（Ｋ＋ＣａＡＴＰ）和延迟整流性钾通道的活性，并观察了ｃｒｏｍａｋａｌｉｍ对缺氧组大鼠钾通道的影响。结果慢性缺氧组大鼠肺动脉平滑肌细胞钙、ＡＴＰ激活性钾通道（Ｋ＋ＣａＡＴＰ）和延迟整流性钾通道的活性均比正常组低，ｃｒｏｍａｋａｌｉｍ可使慢性缺氧组Ｋ＋ＣａＡＴＰ的活性明显增高（Ｐ均＜０．０１）。结论慢性缺氧可明显抑制大鼠肺动脉平滑肌细胞钾通道活性，这可能在慢性缺氧性肺动脉高压的发病机制中发挥重要的作用，钾通道开放剂ｃｒｏｍａｋａｌｉｍ可作为降低缺氧性肺动脉高压的有效药物。Objective To explore the possible effect of potassium channel in chronic hypoxic pulmonary hypertension. Method Male Wistar rats were placed in the identical normobaric or hypoxic environmental chamber. In one chamber, rats were maintained in 10%±0.5% O 2 (by displacement with N 2) for 3 weeks, whereas in the other, rats were maintained in air. The single smooth muscle cell was isolated from pulmonary artery (ψ 200～700 μm) of Wistar rats with acute enzymatic digestion method. Using patch clamp technique, we recorded the outward K + currents in pulmonary artery smooth muscle cells and identified a Ca 2+ . ATP activated K + channel (K + Ca ATP ) and a delayed rectifier K + channel among the outward K + currents. We compared the activities of Ca 2+ .ATP activated K + channel (K + Ca ATP ) or delayed rectifier K + channel in smooth muscle cells isolated from pulmonary artery of chronic hypoxic and normoxic rats. Result The activities of Ca 2+ .ATP activated K + channel (K + Ca ATP ) and delayed rectifier K + channel in chronic hypoxic group are much lower than that in normal group (T test, P <0.01). Cromakalim (10 mmol) caused a marked enhancement of activity of the reduced K + Ca ATP but not the delayed rectifier K + channel in rats of hypoxic group. Conclusion The persistent decrease of potassium channel activity may contribute to setting the development of chronic hypoxic pulmonary hypertension. Cromakalim, one of potassium channel openers, can decrease the pulmonary hypertension induced by chronic hypoxia and may be a new effective drug for treatment of hypoxic pulmonary hypertension.

关 键 词：肺动脉高血 缺氧 钾离子通道 

分 类 号：R543.2[医药卫生—心血管疾病]