【作者】 邓昌磊；

【导师】 肖华军；

【作者基本信息】 第四军医大学 ， 航空、航天与航海医学， 2010， 硕士

【摘要】 随着科技的发展和军队远距投送能力的增强,人们由平原进入高原的速度明显加快,尤其是飞行员、考察或旅游等乘飞机进入高原的人群,不仅会在几个小时内突然暴露于高原低压缺氧环境,机体出现急性高原缺氧,而且需要马上展开工作或次日又要投入飞行,如何保障他们的工作能力和战斗力成为人们关注的热点。权威且成熟的高原阶梯习服和预缺氧训练等措施,由于耗时较长,不适用这种情况。高原供氧则可以通过提高吸入气氧浓度,增加氧分压,改善人体高原缺氧状况,并且具有高效、速效的特点,是急进高原人员较理想的缺氧防护措施。目前采用的高原供氧方式以鼻饲供氧为主,该方法具有节氧、节能的特点,但吸入气氧浓度波动大,而且对鼻黏膜有强烈刺激,舒适性差,影响夜间睡眠。高原富氧室则是通过弥散供氧方式增加室内空气氧浓度来提供人工富氧环境,由于不需佩戴任何吸氧装置,尤其适用于飞行员等,不仅要保证其供氧效果,更要保证其夜间休息和睡眠质量,维持机体体能与功效,确保次日飞行驾驶安全的人群。采用弥散供氧方式的供氧防护效果是肯定的,但由于缺乏针对不同高度和人群的适宜供氧水平、供氧时间等相关研究,至今没有权威的供氧标准和规范,而且目前国内科研多以高压或液氧储气瓶作为富氧室的氧源,这远远不能满足富氧室长时间使用的要求,急需研制出适合高原富氧室使用,可持续、大量弥散供给富氧气体的供氧系统。为此,本文根据西藏自治区高原弥散供氧系统研究和空军高原供氧建设项目的要求和委托,开展了不同供氧水平和供氧方式富氧环境对大鼠急性高原肺水肿防护效果的实验研究。并研究提出了在海拔3500m高原,急进第一天飞行员供氧防护供氧浓度为25%±0.5%〔吸入气氧分压(75±2)mmHg,生理等效高度(2200±150)m〕的标准,并以分子筛变压吸附制氧技术为基础,研制了高原分体式弥散供氧系统,建立了高原富氧室,然后通过人体高原现场实验,对符合该标准富氧室的供氧防护效果进行了评估。研究结果为高原富氧室的推广提供了应用研究基础,为西藏自治区高原弥散供氧系统的技术鉴定和空军高原供氧建设提供了医学实验依据。方法1.动物实验50只雄性Wistar大鼠随机分为地面对照组(C)、缺氧组(H)及富氧组1(OⅠ)、富氧组2(OⅡ)、富氧组3(OⅢ),每组l0只。除C组外,各实验组均以10m/s的速度上升至气压高度6000m,上升同时H组输入空气,OⅠ组和OⅡ组分别输入氧浓度35%和30%的富氧气体,OⅢ组则每4h空气与35%富氧气体交替输入,流量均为7L/min。24h后实验舱下降至地面,处死大鼠,取左肺测含水率,右肺前叶进行病理切片观察,右肺中后叶分别检测肺组织匀浆中的内皮素-1浓度和一氧化氮合酶活力。2.高原现场人体实验研制高原分体式弥散供氧系统,并利用该系统在海拔3500m高原建立氧浓度25.49%±0.26%富氧室(生理等效高度约2100m)。将18名世居平原人员分为平原组(P)、缺氧组(H)和富氧组(O)各6人。P组不进入高原,O组和H组人员乘飞机到达高原后,首先在未供氧情况下记录2组受试人员的心率和SaO2。晚22时至次日9时2组人员分别进入富氧室和普通房间休息,通过睡眠监护仪对受试人员休息期间的SaO2、脉搏波和手动信号进行监测。高原实验同时对P组各项数据在平原进行监测。监测结束后填写睡眠质量调查问卷。结果1.动物实验大鼠肺含水率C组最低(0.80%±0.006%, P<0.01),H组最高(0.83%±0.010%, P<0.01),3个供氧组居中,其中OⅢ组以0.81%±0.007%显著低于OⅠ组和OⅡ组(P<0.05)。一氧化氮合酶活力C组最高〔(1.49±0.24) U/mgpro, P<0.01〕,H组最低〔(0.78±0.28) U/mgpro, P<0.01〕,与H组比较,OⅠ组和OⅢ组NOS活力较强〔(1.06±0.17)mgpro,(1.09±0.20) mgpro, P<0.01〕,OⅡ组差异无显著性。内皮素-1浓度各组间差异无统计学意义。病理结果表明各实验组出现了不同程度肺水肿表现,由重至轻依次为H组、OⅡ组、OⅠ组、OⅢ组。2.高原现场人体实验O组供氧后SaO2为92.3%±1.0%,显著高于供氧前的82.9%±4.2%和H组的79.3%±5.9%(P<0.01),但低于P组的97.3%±0.8%(P<0.05)。睡眠期间呼吸紊乱低通气指数由低至高依次为P组、O组和H组(P<0.05)。心率在O组供氧前后及H组间无显著差异,但均高于P组(P<0.01)。心率变异性分析结果O组和H组的LFn和LF/HF分别为(89.3±2.9) ms2、9.4±2.8和(90.2±1.8) ms2、9.9±1.9,组间无明显差异,但均显著高于P组的(85.8±2.9)ms2和6.4±1.4(P<0.05),同时HFn明显降低。睡眠调查结果显示睡眠质量主观感觉P组最好,O组次之,H组最差。结论在6000m停留24h后大鼠出现了高原肺水肿。氧浓度接近35%富氧环境(生理等效高度约2500m)能够有效预防该肺水肿,而氧浓度30%左右的富氧环境(生理等效高度约3500m)防护效果一般。另外,4h间断供给含氧35%气体同样可以有效预防大鼠在6000m出现的高原肺水肿。如果经过进一步研究能够证实该结论,可以据此制定急进高原人员每天进入富氧室的必要时间,既预防高原病又不影响户外活动。利用我们研制的高原分体式弥散供氧系统在海拔3500m地区成功建立了生理等效高度约2100m的富氧室。该富氧环境能够有效缓解急进高原人员第一天的缺氧反应,提高睡眠质量。同时我们也观察到供氧后O组心率和交感神经兴奋性还处于较高水平,说明人体仍然在进行活跃的代偿反应,仍然在高原习服的进程中。据此,我们认为,一定氧浓度人工富氧环境的应用与高原习服并不矛盾,甚至可以按照个人进入高原的时间长短和习服情况适当调整富氧室氧浓度,既有效对抗缺氧又促进高原习服。更多还原

【Abstract】 With the development of the science and technology as well as the improvement of long distance transport capacity of PLA, the speed that people enter the high altitude has been progressively accelerated, especially those who enter high altitude by air, such as pilots, investigators or travelers, etc., will suddenly expose to the low-pressure and hypoxia environment of high altitude within several hours while have to work immediately or put into flying again next day. To ensure their capacity of work and fighting has become the focus that people pay close attention to. In this situation, the authoritative and traditionary anti-hypoxia methods that laddered high altitude acclimatization and hypoxic training have been already no longer suitable in the case of taking too much time. However, there is a high-efficient and immediate effect anti-hypoxia method that supplying oxygen on high altitude for preventing hypoxia effectively through increasing the oxygen concentration and partial pressure of indoor air, which is suitable for people who enter high altitude emergently. Nowadays, nasal feeding oxygen is the main form of high altitude oxygen supplying for its economy of oxygen and energy. While, the oxygen concentration of inspired air is instable and the stimulant to the mucous membrane of nose is serious, as a result it is so unbearable that people couldn’t get to sleep well at night. The oxygen artificial oxygen enriched environment(AOEE) at high altitude can protect people from high altitude hypoxia without any appliance through improving the oxygen concentration of indoor air, which is especially suitable for the people, such as pilots, because they not only need to guarantee the effect of oxygen supply, but also insure the sleep quality and the efficiency of human body for flight security.It is confirmed that supplying oxygen in diffusion way has extensively effected anti-hypoxia, however, there is no authoritative regulation of it, more research on the suitable oxygen concentration and supplying oxygen time are still on the way. Moreover, domestic study usually takes up with the gas cylinders with the high pressure or the liquid oxygen as the oxygen source of the oxygen enriched room, but it is hardly to meet the request of the oxygen enriched room for long-time usage, so the oxygen-supply system that can continually supply a large amount of oxygen is urgently needed. Consequently, according to the request and commission of the development of the diffusion oxygen-supply system of Tibet Autonomous Region and Air Force contribution project of the high altitude oxygen-supply, we have studied the preventing high altitude pulmonary edema (HAPE) effect of oxygen enriched room that had different oxygen concentration and different time to supply oxygen through the animal model of HAPE. According to the results of animal experiment and our experience of aviation medicine study in decades, we have made the preliminary standard that the oxygen concentration of the oxygen enriched room to prevent pilots who enter 3500m high altitude above sea level emergently from high altitude hypoxia should be 25%±0.5%, which is resulted from oxygen partial pressure of inspired air〔(75±2) mmHg〕and physiologically equivalent altitude〔(2200±150)m〕. Meanwhile, based on the technology of pressure swing adsorption oxygen making of molecular sieve, a new high altitude diffusion oxygen-supply system has been developed. Then, the human subjects experimentation in an oxygen enriched room at high altitude has been taken to evaluate anti-hypoxia effect. The results of this study have offered the foundation of the application of the oxygen enriched room as well as the medical experimental basis for the technical evaluation of the diffusion oxygen-supply system of Tibet Autonomous Region and the high altitude oxygen-supply contribution of Air Force.METHODS1. Animal experiment 50 male Wistar rats were randomly divided into five groups, ground contrasted group(C), hypoxia group (H) , rich oxygen group 1(OⅠ), rich oxygen group 2(OⅡ) and rich oxygen group 3(OⅢ), 10 rats of each group, which were raised to 6000m at the speed of 10m/s in the low-pressure rich oxygen experiment chambers, except group C. Meanwhile, group H was supplied with air, group OⅠand OⅡwere supplied with gas that contain 35% and 30% oxygen respectively, group OⅢwas alternatively supplied air or gas that contain 35% oxygen every 4h with the flow rate of 7L/min. The experiment chambers were put down after 24h, and put the rats to death. The left lung was fetched to examine the water ratio of it, the frontal lobe of right lung was used for pathological observing, the middle and posterior lobe of the right lung were used to detect the concentration of endothelin-1(ET-1) and nitricoxide synthase (NOS) vigor respectively. 2. Human subjects experimentation on the high altitude scene At high altitude of 3500m above sea level, the oxygen enriched room with the oxygen concentration of 25.49%±0.26 % (physiologically equivalent altitude about 2100m) was built by utilizing high altitude diffusion oxygen-supply system. 18 plain residents were divide into three groups with 6 people for each, the rich oxygen group (O), hypoxia group (H) and plain group (P). After the group O and group H reached the high altitude by air, the HR and SaO2 were recorded before oxygen was supplied while group P was stay on the plain. From 22:00 to 9:00 of the next day, when group O and group H have a rest at the oxygen enriched room and normal room respectively, SaO2, pulse wave and hand move signals were monitored by the sleep monitors while all data of group P were monitored on the plain. The sleep quality questionnaire of three groups was asked to complete at the morning.RESULTS1. Animal experiment The water ratio of lung among every group presented the remarkable difference. It is the lowest of ground C’s (0.80%±0.006%, P <0.01), the water ratio of group H was the highest (0.83%±0.010%, P <0.01) and those of the 3 oxygen supplied groups were between two parties. The water ratio of group OⅡwas 0.81%±0.007%, which was obviously lower than group OⅠand OⅢ(P <0.05). Group C was highest〔(1.49±0.24) U/mgpro, P <0.01〕on the vigor of NOS, the NOS vigor of group H was the lowest〔(0.78±0.28 )U/mgpro, P <0.01〕. Compared with the group H, the NOS vigor of group OⅠand OⅢwere more strengthened〔(1.06±0.17)mgpro, (1.09±0.20) mgpro, P <0.01〕, but there were no significant strength of group OⅡ. The ET-1 concentration among every group was no significant difference. The pathology result showed that the rat lung of all the experiment groups obviously presented different degrees of interstitium pulmonary edema for serious degree to light degree was group H, group OⅡ, group OⅠand group OⅢin sequence.2. Human subjects experimentation on the high altitude scene The SaO2 of group O was 92.3%±1.0% after the oxygen was supplied, which was higher than 82.9%±4.2% that before oxygen was supplied and 79.3%±5.9% (P <0.01 ) of group H, but lower than 97.3%±0.8% (P <0.05 ) of the group P. There was no significant difference of HR before and after oxygen was supplied as well as group H, but the HR of group H and group O was higher than that of group P (P <0.01). There was no significant difference of the sleep structure of group O and group H, but compared with group P, the group H and group O had more light sleep and less deep sleep(P <0.01 ). The result of heart rate variability presented that the LFn and LF/HF of group O and group H were (89.3±2.9) ms2, 9.4±2.8 and (90.2±1.8) ms2, 9.9±1.9 respectively, which was no significant difference but higher than (85.8±2.9) ms2 and 6.4±1.4 of group P (P <0.05 ), and the HFn was significant decreased. The results of questionnaire showed that group P had the best sleep quality and group H had the worst one while group O was ordinary.CONCLUSIONThrough the animal experiment, it was observed that rats stayed at 6000m for 24h got serious HAPE and 35% oxygen concentration of oxygen enriched room with oxygen partial pressure of inspired air 70mmHg, physiologically equivalent altitude of 2500m could effectively prevent the HAPE, but it was not obvious of the protection effect of the oxygen enriched room with 30% oxygen concentration (oxygen partial pressure of inspired air of 56mmHg, physiologically equivalent altitude of 3500m). In addition, intermittent supplying of 35% oxygen every 4h could prevent the HAPE of rat effectively as well. If this conclusion could be verified through further research, it would be the basis to determine how long people who enter high altitude emergently should keep in oxygen enriched room on the first day.According to the human subjects experimentation at the 3500m high altitude, the oxygen enriched room with physiologically equivalent altitude of 2500m was successfully built by utilizing the new-type high altitude diffusion oxygen-supply system. It could protect the people who enter high altitude emergently from serious hypoxia, and effectively improve the sleep quality in the first day. But the HR and the sympathetic nerve excitability were still on relatively high-level, which was proved that the compensation and the acclimatization to high altitude was still taken on the body. According the above, it was supposed that oxygen enriched environment and high altitude acclimatization were not contradictory, so that the oxygen concentration of oxygen enriched room could be adjusted according to different situation of individual in order to assure that both the prevention of high altitude hypoxia and the improvement of high altitude acclimatization were effective.更多还原