目的 通过观察不同程度慢性间歇低氧(chronic intermittent hypoxia,CIH)诱发大鼠高血压过程血管活性物质水平动态变化,来探讨CIH诱发高血压发生过程中血管内皮功能改变的作用及在不同程度CIH之间差异性.方法 将168只Wistar大鼠随机分为零暴露组(UD)、不同程度间歇低氧组(重度:IH1、中度:IH2、轻度:IH3)、持续低氧组(CH)、实验对照组(SC)并分别给予不同实验条件,实验前及实验2、4、6、8周测定各组大鼠血压.实验前UD组8只大鼠及2、4、6、8周时其他各组随机抽取8只大鼠处死留取相应标本,测定血清一氧化氮(NO)、内皮型一氧化氮合酶(eNOS)、内皮素1(ET 1).结果 4周开始不同程度间歇低氧组大鼠动脉收缩压均较实验前显著升高(P<0.01),至8周时升高更加明显,血压升高水平与低氧程度呈正相关,IH1组明显高于IH3组(P<0.05),而SC组和CH组无显著变化.IH组大鼠血清ET-1/NO、eNOS随实验时间延长而呈升高/降低趋势,8 周时明显高于/低于SC组(P<0.01)、CH组(P<0.05或P<0.01)、UD组(P<0.01),而SC组无显著变化.CH组大鼠血清NO、eNOS、ET-1随时间变化并不明显.各IH组之间大鼠血清ET-1、NO、eNOS与低氧程度相关,4、6周时IH1组大鼠血清ET-1明显高于IH1、IH2组(P<0.05),8周时IH1组大鼠血清NO、eNOS要明显低于IH3组(P<0.01).大鼠血清NO、eNOS与血压呈负相关(r=-0.519,P<0.01;r=-0.548,P<0.01),ET-1与血压呈正相关(r=0.615,P<0.01).结论 大鼠血管内皮功能改变在CIH诱发大鼠高血压过程中起着重要作用,且血管内皮功能改变引起高血压发生过程中存在明显的低氧程度依赖性和时间过程的规律性.
Objective To observe the change of vasoactive substances during development of hypertension induced by different degrees of chronic intermittent hypoxia (CIH) in rats, evaluate its role in the pathogenesis of CIH-induced hypertension and the differences among different degrees of CIH. Methods 168 Wistar rats were randomly divided into untreated group (UD), various degrees of intermittent hypoxia group ( severe: IH1, moderate: IH2, mild: IH3 ), continuous hypoxia groups ( CH ),sham control group (SC) and were given to different conditions. Blood pressure was observed before experiment and in weeks 2, 4, 6, 8 after the experiment. In UD group 8 rats were killed before experiment, in weeks 2, 4, 6, 8 in each other groups 8 rats were randomly selected and killed, to preserve corresponding specimens and measure nitric oxide (NO), endothelial nitricoxide synthase (eNOS),endothelin-1 (ET-1). Results In week 4, artery systolic blood pressure (SBP) of IH groups increased significantly compared with those before the experiment ( P 〈0.01), in week 8 SBP increased more apparently, the level of blood pressure was positive correlated with degree of hypoxia, IH1 group were significantly higher than IH3 group ( P 〈0.05), while no significant changes were found in the SC group and CH group. In the IH groups, changes in serum ET-1/serum NO and eNOS with experimental time showed increase/decrease trend, in weeks 8 were significantly higher/lower than the SC group ( P 〈0.01) ,the CH group ( P 〈0.05 or P 〈0. 01) and the UD group ( P 〈0.01), while changes in the SC group were not significant. In the CH group, changes in serum NO, eNOS, ET-1 of rats with experiment time were not obvious. Among groups of IH, serum ET-1, NO, eNOS levels were associated with degree of hypoxia, in weeks 4 and 6, serum ET-1 of IH1 group rats was significantly higher than the other two groups ( P 〈0. 05), while in weeks 8, serum NO, eNOS of IH1 group rats was significantly lower