电压门控钾通道在慢性缺氧性肺动脉高压发展中的作用  

Roles of voltage-gated potassium channels in progression of chronic hypoxic pulmonary hypertension

作　　者：柯琴梅[1] 吴霁[1] 杜以梅[2] 田莉[3] 李伟[1] 朱元州[4] 

机构地区：[1]华中科技大学附属协和医院老年病科,湖北武汉430022 [2]华中科技大学附属协和医院心内科,湖北武汉430022 [3]华中科技大学附属协和医院儿科,湖北武汉430022 [4]武汉科技大学附属天佑医院重症医学科,湖北武汉430022

出　　处：《心脏杂志》2013年第4期385-388,共4页Chinese Heart Journal

基　　金：湖北省自然科学基金项目资助(2004ABA191)

摘　　要：目的:探究慢性缺氧对肺动脉平滑肌细胞电压门控钾通道(Kv)的影响及其在慢性缺氧性肺动脉高压发生发展中的作用。方法:50只雄性SD大鼠随机分为常氧对照组(10只)和慢性缺氧5 d、10 d、20 d及30 d组(各10只)。慢性缺氧组大鼠每天在低氧仓中予以缺氧8 h,分别取缺氧5 d、10 d、20 d及30 d的大鼠进行实验。测量平均肺动脉压(mPAP)并应用全细胞膜片钳技术记录肺动脉平滑肌细胞电压门控钾通道电流(I K)。结果:慢性缺氧显著减低大鼠肺动脉平滑肌细胞的I K峰值及I-V曲线漂移。慢性缺氧5 d组肺动脉平滑肌细胞的I K密度及I-V曲线与常氧组均没有显著差异;而慢性缺氧10 d组肺动脉平滑肌细胞的I K密度及I-V曲线与常氧组均有显著差异(P<0.05),随着缺氧时间的延长,I K密度的峰值进一步降低。与常氧组相比较,慢性缺氧10 d组大鼠的mPAP明显增加(P<0.05),随着缺氧时间的增加,mPAP进一步增加;mPAP的增加与I K密度的下降呈负相关(r=-0.89769,P<0.01)。结论:慢性缺氧在引发肺动脉高压的过程中伴随有肺动脉平滑肌细胞Kv通道的活性降低,提示Kv参与了肺动脉高压的发生发展。AIM：To observe the influence of chronic hypoxia on the activity of voltagegated potassium channel in pulmonary artery smooth muscle cells of rats and its roles in the progression of chronic pulmonary hypertension. METHODS： Fifty male Sprague Dawley rats were randomly allocated into normoxic group （n=10） and chronic hypoxic groups. The chronic hypoxic groups were randomly allocated into four subgroups （n=10, respectively） according to the chronic hypoxic periods. The chronic hypoxic subgroups were kept in a hypoxic environmental chamber 8 h/day for 5, 10, 20, and 30 days, respectively, while the normoxic group was kept in room air. The mean pulmonary arterial pressure （mPAP） and the current of voltagegated potassium channel （IK） in pulmonary artery smooth muscle cells were measured using conventional whole cell patchclamp technique. RESULTS： No significant difference was observed in the density of IK （at ＋60 mV） and the IV relationship between normoxic group and the group exposed to chronic hypoxia for 5 days （P〉0.05）, whereas significant differences were found between the normoxic group and the group exposed to chronic hypoxia for 10 days （P〈0.05）. With the prolonged exposure to hypoxia, the peak density of IK decreased gradually at ＋60 mV. In normoxic rats, the mPAP was significantly increased after exposure to chronic hypoxia for 10 days （P〈0.05） and prolonged exposure to hypoxia further increased the mPAP. The mPAP was negatively correlated with the density of IK （r=-089769, P〈0.01）. CONCLUSION： Exposure to chronic hypoxia may cause decreased activity of voltagegated potassium channel, which leads to hypoxic pulmonary vasoconstriction. This mechanism plays an important role in the progression of chronic pulmonary hypertension.

关 键 词：钾通道 慢性缺氧性肺动脉高压 缺氧性肺血管收缩 大鼠 

分 类 号：R543.2[医药卫生—心血管疾病]