大鼠间断低氧-复氧模拟睡眠呼吸暂停综合征模型的建立

Establishment of Sleep Apnea Syndrome Model in Rats Induced by Intermittent Hypoxia Exposure

目的建立大鼠睡眠呼吸暂停综合征(SAS)动物模型。方法SPF雄性SD大鼠50只随机分为正常对照组(NC)、空气模拟2周对照组(2C)、空气模拟4周对照组(4C)、间断低氧-复氧2周组(2H)和间断低氧-复氧4周组(4H)。后4组大鼠进自制低氧舱,2H、4H组每天间断低氧8h,舱内循环充入氮气和氧气,每次循环90s,循环时间自动控制;舱内氧浓度最高21%±0.5%、最低9%±1.5%;2C和4C组充入空气;NC组不进舱。到规定时间后,颈外静脉和颈总动脉插管分别测定右心功能(RVEDP、RVESP、RV±dp/dtmax)和肺、体循环压力(mCAP、mPAP)。并测定(LV+S)/WT和RV/(LV+S)作为左、右心室肥大指标。结果mPAP:2H组较2C组高18.71%,4H组较4C组高16.87%(P均<0.05);4H组RV+dp/dt、RV-dp/dt和RVESP较4C组分别高56.35%、55.43%和36.36%(P均<0.01),较2H组高80.97%、88.85%、19.49%(P均<0.01);2C组、4C组与NC组上述指标各组间均无显著性差异(P均>0.05)。(LV+S)/WT、RV/(LV+S)及mCAP各组间无显著性差异(P均>0.05)。结论本模型操作简便、控制精确、可重复性佳、符合SAS病理生理学特征,是较理想的SAS动物模型。

Objective To establish a sleep apnea syndrome （SAS） model in rats. Methods Fifty male SPF Sprague-Dawley rats were randomly divided into five groups： normal control group （NC）, 2-week and 4-week experimental control groups （2C and 4C）, and 2-week and 4-week intermittent hypoxia groups （2H and 4H）. The rats of 2H and 4H groups were laid in the hypoxic cabin for 8h per day, in which nitrogen and oxygen were input circularly （90s/cycle）. The FiO2max was 21%±0.5% and FiO2min 9%±1.5%. The gas concentration and the cyclic time were automatically controlled. The rats of 2C and 4C groups were in the norrnoxic cabin, NC group in room air. At the experimental end points, the right ventricle functions （RVEDP, RVESP, RV±dp/dt max）, the mean pulmonary arterial pressure （mPAP）, the mean carotid arterial pressure（mCAP）, the weight ratio of left ventricle plus septum to body [（LV＋S）/WT] and of right ventricle to left ventricle plus septum [RV/（LV＋S）] were measured, respectively. Results The mPAPs of 2H group and 4H group were much higher than those of 2C group and 4C group, respectively （P 〈 0.05）. The RV＋dp/dt, RV-dp/dt and RVESP in 4H group were significantly higher than those of 4C and 2H groups（P〈0.01）. The mCAP, RV/（LV＋S） and （LV＋S）/WT among all of the groups were no significantly different （P〉0.05）. Conclusion The sleep apnea syndrome SPF rat model can be successfully established with the method by which operation is convenient, control is precise, repeatability is well and the effects is well consistent with the SAS pathophysiology.