5-羟基癸酸盐对慢性低氧大鼠肺动脉Kv1.5通道表达的影响

摘要

目的:以大鼠为研究对象,研究线粒体ATP敏感性钾通道(mitoKATP)的抑制剂5-羟基癸酸盐(5-HD)对慢性低氧肺动脉高压大鼠的影响及其潜在机制.方法:24只SD雄性大鼠随机分成对照组、低氧组、低氧+5-羟基癸酸盐干预组,每组8只.将低氧组和5-HD干预组大鼠放入常压低氧舱内[O2(10.0%±0.3%)]以建立低氧肺动脉高压模型. 4周后测定平均肺动脉压(mPAP)及右心室与左心室及室间隔的重量比[RV/(LV+S)],并采用RT-PCR及Western blotting技术,分析各组肺动脉Kv1.5 mRNA及蛋白表达.结果:(1) 慢性低氧组大鼠的mPAP及RV/(LV+S)显著高于正常对照组(P<0.05),5-HD干预组mPAP及RV/(LV+S)显著低于低氧组,均P<0.05.(2) 低氧组Kv1.5通道mRNA及蛋白表达显著低于正常组,5-HD组Kv1.5通道表达显著高于低氧组, 均P<0.05.结论:mitoKATP通道的抑制剂5-HD通过降低mPAP及RV/(LV+S),在慢性低氧肺动脉高压中起保护作用.mitoKATP通道的抑制及Kv1.5通道表达的上调可能与该保护作用有关.%AIM : To investigate the effect of mitochondrial ATP - sensitive potassium channel( mitoKATP ) inhibitor 5 - hydroxydecanoate ( 5 - HD ) on chronic hypoxic pulmonary artery hypertension ( CHPAH ) in rats. METHODS :Twenty - four male Sprague - Dawley rats were randomly divided into 3 groups :control group, hypoxia group and hypoxia +5 - HD group.To establish an animal model of CHPAH, the rats in hypoxia group and hypoxia +5 - HD group were placed into a hypoxic and normoharic chamber [ O2( 10.0 ±0.3 )％] for 4 weeks ( 8 h a day, 6 days a week ).The mean pulmonary arterial pressure ( mPAP ) and the ratio of right ventricle weight to left ventricle with septum weight [ RV/( LV + S ) ]were measured.Western blotting and reverse transcription - polymerase chain reaction ( RT - PCR ) were performed to analyze the protein and mRNA levels of Kv1.5 in the pulmonary artery , respectively.RESULTS : The mPAP and RV/( LV +S ) were much higher in hypoxia group than those in control group, while those in hypoxia +5 - HD group were decreased as compared to hypoxia group.The protein and mRNA levels of Kv1.5 in hypoxic group were signific:antly lower than those in control group, and this decrease was partly reversed by 5 - HD.CONCLUSION : 5 - HD may exert a protective effect on CHPAH by decreasing mPAP and RV/ ( LV + S ).Inhibiting mitoKATP and stimulating Kv1.5 expression by 5 - HD may contribute to the mechanism of this effect.