正加速度和噪声复合应激对大鼠学习记忆的影响
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摘要
现代战争由于其特殊性，对参战双方部分人员的精神和心理状态有着一定的损害作用和后遗影响。应激刺激的形式很多，恐惧、疼痛、缺氧、高温、寒冷、加速度、噪声等都是应激源。在军事医学领域中，应激对部队作战人员的不利影响日益凸现，并逐渐引起军事医学工作者的高度重视。
由于军事飞行特殊的工作环境，战斗机飞行员不可避免地暴露于各种应激源，其中最常见的主要有正加速度(+Gz)、噪声、振动和高温等，已成为威胁飞行安全的重要因素。现代高性能战斗机具有很高的机动性能，其在飞行中产生的正加速度可高达+gGz，持续时间可达15～45s，并可反复出现，已超出了人体正常的耐受限度。学习与记忆是动物和人类赖以生存所不可或缺的重要脑功能，可以反映神经系统的功能状态。以往的研究工作已证实，高G值持续性正加速度暴露可引起动物脑损伤和学习记忆功能障碍，一定强度的噪声可引起人和动物学习记忆能力降低。然而，有关正加速度和噪声复合应激因素对脑的影响与防护措施尚未见研究报道。因此，阐明上述复合应激因素作用后飞行人员工作能力的变化规律，对进一步做好飞行卫生保障工作具有重要的现实意义。本研究观察
第四军医大学硕士学位论文
了正加速度和噪声复合应激对大鼠学习记忆功能的影响，旨在揭示
正加速度和噪声复合应激后大鼠学习记忆功能的变化规律，并进一
步探讨低G锻炼是否对正加速度和噪声复合应激造成的学习记忆
功能障碍具有保护作用。
本研究选用我校动物实验中心提供的雄性SD大鼠，在动物离
心机上进行招z暴露，同时利用白噪声发生器产生噪声。通过Y-
型迷宫实验、避暗实验、旷场分析实验，分别在复合应激暴露后的
即刻、2d、4d和6d，观察不同正加速度和噪声复合应激条件下大
鼠学习和记忆功能的变化情况。
本研究的主要结果及发现如下:
1.高+Gz和噪声复合应激可引起大鼠持续性学习记忆功能障
碍本实验观察了+10Gz/3min和godB(A)/3 omin噪声复合应激对
大鼠学习记忆功能的影响。结果发现，复合应激组大鼠正确率在暴
露后各时间点较对照组和噪声组均显著降低(P<0.01)，反应时均
显著延长(P<0.01);中央格停留时间在暴露后即刻较对照组和噪
声组显著延长(P<0.01);总时间和错误数在暴露后即刻较对照组
显著增加(P<0.01)，潜伏期在暴露后即刻显著缩短(P<0.01)，在
暴露后6d时仍较对照组显著缩短(P<0.01)。而与+l OGz组相比，
复合应激组大鼠正确率在暴露后即刻显著降低(P<0.05)，反应时
显著延长(P<0.01)。结果提示，+10Gz/3min和90dB(A)/30min
噪声复合应激可引起大鼠持续性学习记忆功能障碍，两种因素具有
协同效应，其中+Gz为主要影响因素。
2.短时重复高+Gz暴露复合噪声应激可引起大鼠持续性学习
记忆功能障碍本实验观察了重复5次+l 002/455暴露复合
90dB(A)/30min噪声应激对大鼠学习记忆功能的影响。结果发现，
复合应激组大鼠正确率在暴露后各时间点较对照组均显著降低(P
<0.01)，反应时均显著延长(P<0.01):总时间和错误数在暴露后
即刻显著增加(P<0.01)。与+Gz重复暴露组相比，复合应激组大
鼠正确率在暴露后各时间点均显著降低(P<0.01)，反应时在暴露
第四军医大学硕士学位论文
后4d及6d显著延长(P<0.01);总时间和错误数在暴露后即刻显
著增加(P<0.01)。结果提示，重复5次+1 OGz/455暴露复合
90dB(A)/3 omin噪声应激可引起大鼠持续性学习记忆功能障碍。
3.低G锻炼对高玲z和噪声复合应激所致大鼠学习记忆功能障
碍具有保护作用本实验在复合应激暴露之前，预先进行连续3天
(l次/d)的+4G/3min的低G锻炼，观察再暴露于高玲z和噪声复合
应激时大鼠学习记忆功能的变化。结果发现，复合应激组大鼠反应
时在暴露后各时间点较对照组均显著延长(P<0 .01)，正确率均显
著下降(P<0 .01);锻炼组大鼠反应时仅在暴露后即刻较对照组显著
延长(P<0 .05)，而与复合应激组比较，锻炼组大鼠反应时在暴露后
各时间点均显著缩短(P<0 .01)，正确率均显著升高(P<0 .01)。复合
应激组大鼠总时间和错误数较对照组显著增加(P<0 .01)，潜伏期显
著缩短(P<0 .01);锻炼组大鼠总时间和错误数较复合应激组显著减
少(P<0.01)，潜伏期显著延长(P<0 .01)。结果提示，连续3天的
+4G/3min(l次/d)锻炼对+10Gz/3min复合godB(A)/30min噪声应
激所致的大鼠学习记忆功能障碍具有一定的保护作用。
总之，本研究利用动物离心机和白噪声发生器，观察了正加速
度和噪声复合应激后大鼠学习记忆能力的变化情况及其与复合应
激强度的关系，主要阐明了以下问题:高+Gz和噪声复合应激可
引起大鼠持续性学习记忆功能障碍，短时重复高+Gz暴露复合噪
声应激亦可引起大鼠持续性学习记忆功能障碍，低G锻炼对正加速
度和噪声复合应激所致的大鼠学习记忆功能障碍具有一定的保护
作用。本研究为进一步做好飞行卫生保障工作，制定安全有效的防
护措施提供了实验依据和理论指导。
Due to it's speciality, modern war has negative impact on mental and psychological stability of military personnel of both sides. There are a number of types of stressors taking different forms such as horror, pain, anoxia, hyperthermia, coldness, acceleration, noise and so on. In field of military medicine, harmful effects caused by stress on army men are becoming more and more important and drawing greater attention from military medical specialists than ever before. Because of their special working environment, pilots have been inevitably exposed to various stressors among which positive acceleration (+Gz), noise, vibration and high temperature are always present and remain important factors threatening flying safety. Modern high-performance aircraft has good maneuverability. The positive acceleration produced by aircraft can reach +9Gz, last for 15s to 45s, and always repeatedly occur. This may exceed physiological tolerance of human beings. Learning and memory are extremely important brain functions for
animal and human being, and they can reflect the normal function of central nervous system. According to previous study, exposure to sustained acceleration may cause impairment of learning and memory, exposure to noise can give rise to the deterioration of learning and
memory. However, effects of +Gz and noise combined stress on pilots have not been reported yet. So, it's of great practical significance to explore the effects of combined stress on pilot's working capacity, and this may be very useful to improve flying safety. This study has observed changes of learning and memory in rats after different +Gz and noise combined stresses exposure. The purpose of the present study was to find out the characteristics of changes of learning and memory after +Gz and noise combined stress exposure, and to further verify whether lower G training can provide protection against learning and memory impairment after this combined stress exposure.
Male Sprague-Dawley rats (offered by animal experimental center of the Fourth Military Medical University) were exposed to +Gz on animal centrifuge and to noise produced by white noise generator. Changes of learning and memory in rats were observed at the time of immediately, 2d, 4d and 6d after different +Gz and noise combined stress exposure by use of Y-maze test, step-through test, and open field test.
The main findings are as follows:
1. High +Gz and noise combined stress may cause sustained impairment of learning and memory in rats. We investigated the effects of 4-10Gz/3min and 90dB/30min combined stress on learning and memory in rats. The results showed that, as compared with control group and noise group, the percentage of right reactions decreased significantly (P < 0.01) and the reaction time increased significantly (p < 0.01) in +Gz and noise combined stress group at all time after stress; time stay in center grille increased significantly immediately after stress exposure(P < 0.01). When compared with control group , total time and number of error increased significantly (p < 0.01) while latent
time decreased significantly immediately and 6 days after stress exposure(P < 0.01). As compared with +10Gz group, number of correct reaction in combined stress group decreased significantly (P < 0.05) and reaction time increased significantly (P < 0.01) immediately after stress exposure. It suggested that +Gz and noise combined stress may impair learning and memory of rats, and +Gz seems to contribute more to the combined effects.
2. Repeated short-term high +Gz combined noise stress may lead to sustained impairment of learning and memory in rats. We investigated the effects of repeated 5 times +10Gz /45 s and noise (90dB(A)/30min) combined stress on learning and memory in rats. The results showed that, as compared with control group, percentage of right reactions decreased significantly (P < 0.01) and reaction time increased significantly (P < 0.01) in combined stress group at all time after stress exposure; total time and number of errors increased significantly (P < 0
由于军事飞行特殊的工作环境，战斗机飞行员不可避免地暴露于各种应激源，其中最常见的主要有正加速度(+Gz)、噪声、振动和高温等，已成为威胁飞行安全的重要因素。现代高性能战斗机具有很高的机动性能，其在飞行中产生的正加速度可高达+gGz，持续时间可达15～45s，并可反复出现，已超出了人体正常的耐受限度。学习与记忆是动物和人类赖以生存所不可或缺的重要脑功能，可以反映神经系统的功能状态。以往的研究工作已证实，高G值持续性正加速度暴露可引起动物脑损伤和学习记忆功能障碍，一定强度的噪声可引起人和动物学习记忆能力降低。然而，有关正加速度和噪声复合应激因素对脑的影响与防护措施尚未见研究报道。因此，阐明上述复合应激因素作用后飞行人员工作能力的变化规律，对进一步做好飞行卫生保障工作具有重要的现实意义。本研究观察
第四军医大学硕士学位论文
了正加速度和噪声复合应激对大鼠学习记忆功能的影响，旨在揭示
正加速度和噪声复合应激后大鼠学习记忆功能的变化规律，并进一
步探讨低G锻炼是否对正加速度和噪声复合应激造成的学习记忆
功能障碍具有保护作用。
本研究选用我校动物实验中心提供的雄性SD大鼠，在动物离
心机上进行招z暴露，同时利用白噪声发生器产生噪声。通过Y-
型迷宫实验、避暗实验、旷场分析实验，分别在复合应激暴露后的
即刻、2d、4d和6d，观察不同正加速度和噪声复合应激条件下大
鼠学习和记忆功能的变化情况。
本研究的主要结果及发现如下:
1.高+Gz和噪声复合应激可引起大鼠持续性学习记忆功能障
碍本实验观察了+10Gz/3min和godB(A)/3 omin噪声复合应激对
大鼠学习记忆功能的影响。结果发现，复合应激组大鼠正确率在暴
露后各时间点较对照组和噪声组均显著降低(P<0.01)，反应时均
显著延长(P<0.01);中央格停留时间在暴露后即刻较对照组和噪
声组显著延长(P<0.01);总时间和错误数在暴露后即刻较对照组
显著增加(P<0.01)，潜伏期在暴露后即刻显著缩短(P<0.01)，在
暴露后6d时仍较对照组显著缩短(P<0.01)。而与+l OGz组相比，
复合应激组大鼠正确率在暴露后即刻显著降低(P<0.05)，反应时
显著延长(P<0.01)。结果提示，+10Gz/3min和90dB(A)/30min
噪声复合应激可引起大鼠持续性学习记忆功能障碍，两种因素具有
协同效应，其中+Gz为主要影响因素。
2.短时重复高+Gz暴露复合噪声应激可引起大鼠持续性学习
记忆功能障碍本实验观察了重复5次+l 002/455暴露复合
90dB(A)/30min噪声应激对大鼠学习记忆功能的影响。结果发现，
复合应激组大鼠正确率在暴露后各时间点较对照组均显著降低(P
<0.01)，反应时均显著延长(P<0.01):总时间和错误数在暴露后
即刻显著增加(P<0.01)。与+Gz重复暴露组相比，复合应激组大
鼠正确率在暴露后各时间点均显著降低(P<0.01)，反应时在暴露
第四军医大学硕士学位论文
后4d及6d显著延长(P<0.01);总时间和错误数在暴露后即刻显
著增加(P<0.01)。结果提示，重复5次+1 OGz/455暴露复合
90dB(A)/3 omin噪声应激可引起大鼠持续性学习记忆功能障碍。
3.低G锻炼对高玲z和噪声复合应激所致大鼠学习记忆功能障
碍具有保护作用本实验在复合应激暴露之前，预先进行连续3天
(l次/d)的+4G/3min的低G锻炼，观察再暴露于高玲z和噪声复合
应激时大鼠学习记忆功能的变化。结果发现，复合应激组大鼠反应
时在暴露后各时间点较对照组均显著延长(P<0 .01)，正确率均显
著下降(P<0 .01);锻炼组大鼠反应时仅在暴露后即刻较对照组显著
延长(P<0 .05)，而与复合应激组比较，锻炼组大鼠反应时在暴露后
各时间点均显著缩短(P<0 .01)，正确率均显著升高(P<0 .01)。复合
应激组大鼠总时间和错误数较对照组显著增加(P<0 .01)，潜伏期显
著缩短(P<0 .01);锻炼组大鼠总时间和错误数较复合应激组显著减
少(P<0.01)，潜伏期显著延长(P<0 .01)。结果提示，连续3天的
+4G/3min(l次/d)锻炼对+10Gz/3min复合godB(A)/30min噪声应
激所致的大鼠学习记忆功能障碍具有一定的保护作用。
总之，本研究利用动物离心机和白噪声发生器，观察了正加速
度和噪声复合应激后大鼠学习记忆能力的变化情况及其与复合应
激强度的关系，主要阐明了以下问题:高+Gz和噪声复合应激可
引起大鼠持续性学习记忆功能障碍，短时重复高+Gz暴露复合噪
声应激亦可引起大鼠持续性学习记忆功能障碍，低G锻炼对正加速
度和噪声复合应激所致的大鼠学习记忆功能障碍具有一定的保护
作用。本研究为进一步做好飞行卫生保障工作，制定安全有效的防
护措施提供了实验依据和理论指导。
Due to it's speciality, modern war has negative impact on mental and psychological stability of military personnel of both sides. There are a number of types of stressors taking different forms such as horror, pain, anoxia, hyperthermia, coldness, acceleration, noise and so on. In field of military medicine, harmful effects caused by stress on army men are becoming more and more important and drawing greater attention from military medical specialists than ever before. Because of their special working environment, pilots have been inevitably exposed to various stressors among which positive acceleration (+Gz), noise, vibration and high temperature are always present and remain important factors threatening flying safety. Modern high-performance aircraft has good maneuverability. The positive acceleration produced by aircraft can reach +9Gz, last for 15s to 45s, and always repeatedly occur. This may exceed physiological tolerance of human beings. Learning and memory are extremely important brain functions for
animal and human being, and they can reflect the normal function of central nervous system. According to previous study, exposure to sustained acceleration may cause impairment of learning and memory, exposure to noise can give rise to the deterioration of learning and
memory. However, effects of +Gz and noise combined stress on pilots have not been reported yet. So, it's of great practical significance to explore the effects of combined stress on pilot's working capacity, and this may be very useful to improve flying safety. This study has observed changes of learning and memory in rats after different +Gz and noise combined stresses exposure. The purpose of the present study was to find out the characteristics of changes of learning and memory after +Gz and noise combined stress exposure, and to further verify whether lower G training can provide protection against learning and memory impairment after this combined stress exposure.
Male Sprague-Dawley rats (offered by animal experimental center of the Fourth Military Medical University) were exposed to +Gz on animal centrifuge and to noise produced by white noise generator. Changes of learning and memory in rats were observed at the time of immediately, 2d, 4d and 6d after different +Gz and noise combined stress exposure by use of Y-maze test, step-through test, and open field test.
The main findings are as follows:
1. High +Gz and noise combined stress may cause sustained impairment of learning and memory in rats. We investigated the effects of 4-10Gz/3min and 90dB/30min combined stress on learning and memory in rats. The results showed that, as compared with control group and noise group, the percentage of right reactions decreased significantly (P < 0.01) and the reaction time increased significantly (p < 0.01) in +Gz and noise combined stress group at all time after stress; time stay in center grille increased significantly immediately after stress exposure(P < 0.01). When compared with control group , total time and number of error increased significantly (p < 0.01) while latent
time decreased significantly immediately and 6 days after stress exposure(P < 0.01). As compared with +10Gz group, number of correct reaction in combined stress group decreased significantly (P < 0.05) and reaction time increased significantly (P < 0.01) immediately after stress exposure. It suggested that +Gz and noise combined stress may impair learning and memory of rats, and +Gz seems to contribute more to the combined effects.
2. Repeated short-term high +Gz combined noise stress may lead to sustained impairment of learning and memory in rats. We investigated the effects of repeated 5 times +10Gz /45 s and noise (90dB(A)/30min) combined stress on learning and memory in rats. The results showed that, as compared with control group, percentage of right reactions decreased significantly (P < 0.01) and reaction time increased significantly (P < 0.01) in combined stress group at all time after stress exposure; total time and number of errors increased significantly (P < 0
引文
1．陈宜张．内环境稳定与神经内分泌功能．见：韩济生．神经科学原理．北京：北京医科大学出版社，1999：857—877
2. Sun XQ, Zhang LF, Wu XY, Jiang SZ. Effect of repeated +Gz exposures on energy metabolism and some ion contents in brain tissues of rats. Aviat Space Environ Med, 2001, 72(5): 422-426
3. Schwertner HA, Blum K, Wallace JE, Eubanks JD. Alterations in brain electrolytes during acceleration in mice. Aviat Space Environ Med, 1977, 48(8): 705-707
4．孙喜庆，李靖，吴兴裕．+Gz重复暴露对兔脑组织Fos蛋白表达的影响．航天医学与医学工程，2002，15(1)：17-21．
5．孙喜庆，张立藩，马丹，吴兴裕，姜世忠，章志红．+Gz重复暴露对大鼠脑组织一氧化氮合酶分布的影响．中华航空医学杂志，1996，7(4)：228-231
6. Morreale de Escobar G, Escobar F.Thyroid horm one and the developing brain. In: bussault Walker PJH. Eds. Congenital Hypothyroidism. Marces Dekker Inc, Butterworths. New York, 1983:85-126
7. Arnsten AF, Goldman-Rakic PS. Noise stress impairs prefrontal cortical cognitive function in monkeys: evidence for a hyperdopaminergic mechanism. Arch Gen Psychiatry, 1998, 55(4): 362-368
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