阻塞性睡眠呼吸暂停综合征小型猪模型实验研究

以间歇性低压低氧方法建立阻塞性睡眠呼吸暂停综合征(Obstructivesleepapneasyndrome,OSAS)小型猪模型。8只小型猪编号后随机分为A、B、C组。A为对照组,置于双室低压氧仓二室,维持海平面压力;B、C组置于双室低压氧仓一室,仓内压力约53.9KPa、氧浓度10%~11.2%。3组每天均入仓6h。第13d处死B组,A、C组第23d同时处死。各组进仓前和处死前均行咽部CT扫描、口咽部呼吸压力、血氧饱和度检查;处死后取咽部组织行病理检查。咽部CT扫描示,咽部舌骨水平咽后壁厚度和侧壁厚度,进仓第13d(8.8±1.1vs6.5±0.6,8.1±0.2vs6.3±0.6)和第23d(9.2±1.2vs6.3±0.7,8.9±0.7vs6.4±0.5)均较进仓前有增加(P<0.05)。舌骨水平左右径和软腭水平前后径进仓第13d(7.6±1.4vs9.7±1.4,3.8±1.1vs6.5±1.3)和第23d(6.4±1.6vs9.3±1.5,4.3±0.9vs5.9±0.8)均较进仓前减小(P<0.05)。舌骨后区前后径进仓第23d后较进仓前减小(3.7±0.9VS6.4±0.6,P<0.05)。进仓第23d口咽呼吸压力(0.0755Mv)较进仓前(0.0658Mv)明显增大(P<0.05),而第13d(0.063Mv)较进仓前变化不明显。血氧饱和度进仓第13d(87%)和第23d(88.5%)均较进仓前(96.3%)明显减小(P<0.05)。病理变化:A组:咽部黏膜为复层扁平上皮,黏膜下层薄,肌层横纹清、肌间脂肪少。B组:咽部上皮组织增生伴角化,黏膜下层水肿纤维组织增生,肌层厚横纹不清、肌间脂肪灶性浸润;C组较B组病理变化程度加重。提示:间歇性低压低氧,使小型猪咽腔组织结构和力学特性发生类似OSAS病人的变化,本研究建立的OSAS小型猪模型,能用于人OSAS的进一步研究。

An Experimental Study on the Mini Pig Model of Obstructive Sleep Apnea Syndrome

A mini pig model for study of human obstructive sleep apnea syndrome (OSAS) was established by altitude hypoxia. Eight mini pigs were randomly assigned to 3 groups, named A, B, and C. They were placed in a double-roomed altitude chamber. As control, Groups A lived in Room 2 and there was an altitude of sea level in it. Groups B and C were in Room 1 and the pressure in it was 53.9 KPa with an oxygen concentration of 10.0%-11.2%. All of these mini pigs were in their rooms for 6 hours per day. Pigs in Groups B were in the room for 12 consecutive days and sacrificed on the 13th day. Pigs in Groups A and C were executed on the 23rd day. The pharyngeal CT scanning and the defermination of respiratory pressure in pharynx oralis and saturation of arterial blood oxygen were conducted in all exprimental mini pigs before they were put in chamber and before they were put to death. The pharyngeal tissues of the executed pigs were pathologically examined. CT scanning revealed there was significant (P < 0.05) increase in mini pigs' posterior pharyngeal wall (8.8 +/- 1.1 vs 6.5 +/- 0.6) and lateral pharyngeal wall (8.1 +/- 0.2 vs 6.3 +/- 0.6) on the 13th day as compared with that before they were put in chamber, and there was also significant (P < 0.05) increase (9.2 +/- 1.2 vs 6.3 +/- 0.7; 8.9 +/- 0.7 vs 6.4 +/- 0.5) on the 23rd day. There was significant (P < 0.05) reduction in diameter from left to right at the hyoid bone level (7.6 +/- 1.4 vs 9.7 +/- 1.4) and in the anteroposterior diameter at the soft palace level (3.8+/-1.1 vs 6.5 +/- 1.3) on the 13th day as compared with that before the mini pigs were put in chamber, and there was also sinificant (P < 0.05) reduction (6.4 +/- 1.6 vs 9.3 +/- 1.5; 4.3 +/- 0.9 vs 5.9 +/- 0.8) on the 23rd day. There was significant reduction (P < 0.05) in anteroposterior diameter on the posterior area of hyoid bone (3.7 +/- 0.9 vs 6.4 +/- 0.6) on the 23rd day. A significant change (P < 0.05) was observed in respiratory pressure of pharynx oralis on the 23rd day (0.0755 Mv) when compared with that before the first day (0.0658 Mv) in chamber and no significant change was seen on the 13th day. The saturation of blood oxygen decreased from 96.3% to 87.0% on the 13th day (P < 0.05) and further descended to 88.5% on the 23rd day (P < 0.05), compared with that before the first day in chamber. Pathological examination showed. In Group A, the mucosa of pharynx is covered by nonkeratinized-stratified squamous epithelium, and the layer of submucosa is thin; the muscular layer has clear striations and less fat cells among muscular fibers. In Group B, the pharyngeal epithelium is cornified and proliferated. Edema and proliferation of connective tissue occur in submucosa, and the muscular layer is thick with unclear striations; local infiltration of fat cells can be observed among muscular fibers. The pathological changes were more serious in Group C than in Group B. The results suggest that the method of intermittent altitude hypoxia could make the pharyngeal tissue of mini pig remodel and change its muscular biomechanical properties into those similar to the performance of OSAS in human. Living in altitude hypoxia for 22 days, the mini pigs became ill with OSAS, thus the expected animal model has been established in this study and could be used in further researches on OSAS in patients.