慢性间歇低氧对大鼠血压和交感神经兴奋性的影响

The effects of chronic intermittent hypoxia on blood pressure and sympathetic nerve activity in rats

目的通过观察不同程度慢性间歇低氧（chronic intermittent hypoxia，CIH）作用下大鼠血压与交感神经活性水平动态变化，探讨CIH对血压及交感神经活性的影响及血压与交感神经活性之间的相关性，并明确CIH诱发高血压发病的机制。方法168只雄性6周龄Wistar大鼠，体重160—180g，采用随机数字表法分为非暴露组（UD）、重度间歇低氧组（IH1）、中度间歇低氧组（IH2）、轻度间歇低氧组（IH，）、持续低氧组（CH）及对照组，分别给予不同程度和频率的低氧环境。UD组8只大鼠于实验前处死，其余各实验组每组32只大鼠，分别于2、4、6、8周时随机抽取8只处死，留取静脉血抗凝离心后一80℃保存血浆，并于实验前、实验结束后分别测定动脉收缩压，实验结束后测定血浆中去甲肾上腺素（norepinephrine，NE）。结果各组大鼠实验前收缩压差异无统计学意义（F=0．008，P〉0．05），随着实验时间延长，各间歇低氧组大鼠收缩压逐渐升高，4周开始明显高于UD组、对照组及CH组（均P〈0．05）且血压水平与低氧程度正相关（F=9．844，P〈0.01），IH、组明显高于IH，组（P〈0．05），而对照组和CH组无明显改变。各间歇低氧组大鼠血浆NE随实验时间延长而逐渐升高，8周时明显高于UD组、SC组及CH组（均P〈0．05或P〈0．01），且NE水平与低氧程度正相关（F=11．537，P〈0．01），IH，组明显高于IH，组（P〈0．05），sC组和CH组大鼠血浆NE变化不显著。大鼠血浆NE与血压呈显著正相关（r=0．538，P〈0．01）。结论CIH作用可以引起大鼠血压增高和交感活性增强且存在明显的低氧程度依赖性和时间过程规律性，推测CIH引起大鼠血压增高可能与交感活性增强相关。

Objective To observe the changes of blood pressure and sympathetic nerve activity under different degrees of chronic intermittent hypoxia （CIH） in rats, and therefore to explore the effects of CIH on blood pressure and sympathetic nerve activity and the correlation between blood pressure and sympathetic nerve activity in the pathogenesis of CIH-induced hypertension. Methods Male Wistar rats （n =168） were randomly divided into untreated group （UD）, severe intermittent hypoxia group （IH1 ）, moderate intermittent hypoxia group （IH2 ）, mild intermittent hypoxia group （IH3 ）, continuous hypoxia group （CH）, sham control group （SC） and were exposed to different conditions. Rats （n = 8 ） of the UD group were sacrificed before the experiment, while rats of the other groups were killed in weeks 2, 4, 6, and 8 of the experiment. Anticoagulated venous blood was obtained and plasma was stored at - 80 ℃. Systolic arterial pressure （SBP） was recorded before and after the experiment, while plasma norepinephrine （NE） was measured after the experiment. Results Before the experiment, the SBP of rats showed no significant differences among groups （ F = 0. 008, P 〉 0. 05 ） , but the SBP of rats in the intermittent hypo^a groups increased gradually, and higher than the UD group, the SC group and the CH group from the beginning of week 4 （ P 〈 0. 05 or P 〈 0. 01 ）. The blood pressure was positively related with the degree of hypoxia （ F = 9. 844, P 〈 0.01 ）, and that of the IH1 group was significantly higher than that of the IH3 group （ P 〈 0.05 ）, while no significant changes were found in the SC and the CH groups. The plasma NE level of rats in the intermittent hypoxia groups increased gradually with the experiment and significantly higher than that of the UD group, the SC group and the CH group at week 8 （ P 〈 0.05 or P 〈 0. 01 ） , and the level of NE was positively related with the degree of hypoxia （ F = 11. 537, P 〈 0. 01 ）. The NE level of the IH~ group was significantly higher than that of the IH3 group （ P 〈 0. 05 ）, but no significant change was found in the SC and the CH groups. The plasma NE levels were positively related with blood pressure （ r = 0. 530, P 〈 0. 01 ）. Conclusions CIH can cause increased blood pressure and sympathetic activity in rats, and the effect was dependent on the degree of hypoxia and the time of exposure. The results suggested that CIHinduced higher blood pressure was associated with increased sympathetic activity.