慢性心理应激对大鼠心理行为和神经内分泌免疫的影响
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摘要
[目的]通过观察慢性心理应激对大鼠行为、学习记忆能力的影响以及血清中IL-1p、IL-2、ACTH、CORT水平以及脑组织中5-HT表达的变化,探讨慢性心理应激对大鼠心理行为、免疫功能和神经内分泌的影响及其可能的影响机制。通过通径分析探讨行为、免疫与神经内分泌指标之间的相互关系,从免疫神经内分泌网络学的视角出发进一步阐明心理应激发病机理,为防治心身疾病、亚健康提供新的思路和理论依据。
[方法]选取健康成年的SD大鼠20只,雌雄各半,随机分为正常对照组和慢性应激组,每组10只。采用4种应激方式建立慢性应激动物模型。在应激过程中每周检测动物的体重及旷场实验得分。1.应激结束后,采用旷场实验、悬尾实验以及Morris水迷宫实验检测大鼠心理行为及学习记忆能力的变化；2.断头处死后取血清采用ELISA方法检测IL-1β、IL-2水平,采用放射免疫方法检测ACTH、CORT的含量；3.取脑组织切片采用免疫组织化学ABC法检测5-HT的表达。
[结果]1.大鼠体重及行为学测试：1)两组雄性大鼠的体重均随时间的增加而增加,但慢性应激组大鼠第2、3、4、5周末体重均低于对照组(P<0.05)。两组雌性大鼠体重也随时间的增加而增加,第5周末应激组大鼠的体重低于对照组(P<0.05)；2)慢性应激组大鼠旷场实验水平得分、垂直得分和总分均随时间呈下降趋势。与正常对照组相比,慢性应激组大鼠第3、4、5周末水平得分、垂直得分和总分均降低(P<0.05)。与正常对照组相比,慢性应激组大鼠中央格停留时间随时间呈上升趋势,且第3、4、5周末中央格停留时间延长(P<0.05)；3)悬尾实验中,慢性应激组大鼠的不动时间延长(P<0.01)；4)4天的Morris水迷宫定位航行实验中,两组大鼠的平均潜伏期(LT)均呈下降趋势,但与正常对照组相比,慢性应激组大鼠从第二天开始,LT均延长(P<0.05)。在空间搜索实验中,与正常对照组相比,慢性应激组大鼠穿越原平台的次数减少,原平台象限的游泳距离及游泳总距离明显缩短(P<0.05)。
2.慢性心理应激对大鼠神经内分泌免疫的影响：1)慢性应激组大鼠血清IL-1p、IL-2的含量均低于正常对照组(P<0.01)。慢性应激组大鼠胸腺指数和脾脏指数与正常对照组相比差异无统计学意义(P>0.05)；2)与对正常照组相比,慢性应激组大鼠血清CORT、ACTH的含量均升高(P<0.01)。慢性应激后雄性大鼠血清ACTH含量比雌性大鼠高(P<0.05)；3)与正常对照组相比,慢性应激组大鼠海马锥体细胞间隙增大,排列疏松不齐,5-HT表达减少。4)Pearson相关分析显示慢性应激时大鼠血清IL-1p、IL-2的含量与血清CORT、ACTH的含量呈负相关。
3.通径分析结果显示大鼠血清IL-1p的含量与旷场实验总分呈正相关；IL-2的含量与LT、不动时间呈负相关,与旷场实验总分呈正相关；CORT的含量与LT、不动时间呈正相关,与旷场总分呈负相关。
[结论]慢性心理应激在心理行为方面可以导致机体焦虑、抑郁、行为异常、以及学习记忆能力的减退；在生理方面抑制体重的增长,降低大鼠血清IL-1β、IL-2的水平,升高血清ACTH、CORT水平,激活HPA轴,引起HPA轴功能亢进,可能导致机体免疫力下降,引发心身疾病。心理行为与内分泌免疫之间的相互关系,提示慢性心理应激时机体免疫内分泌与心理行为之间存在相互调节和相互作用。
[Objective] To study the effects of chronic psychological stress on behaviors, and learning and memory abilities, and immunological function, and neuroendocrine function, and to improve the important and scientific basis for intervention in sub-health.
[Methods] 20 SD rats, adult and health, were randomly divided into control group and chronic stress group(n=10 in each group).The rat mode of stress was made by different multi-stress,4 weeks running. After stress, the Open-field test, Morris water maze test and suspend tail test were performed to test the change of mood and behaviors, and learning and memory abilities of rats. After the experiment, thymus index and spleen index were measured. ELISA was applied to measure levels of interleukine-1β(IL-1β) and interleukine-2(IL-2) in blood serum. RIA was applied to measure levels of ACTH and CORT in blood serum. Expression of 5-HT in neural cells in rats'brain tissue were measured with ABC of immunohistoc-hemical method.
[Results] Chronic stress significantly suppressed body weight gain. The increases of body weight in the chronic group were significantly lower than that in the control group. Compared with the control group, the chronic stress group had relatively fewer crossing scores, and rearing scores, and total scores. In suspend tail test, the chronic group had relatively longer staying time. In hidden-platform training of Morris water maze, the mean escape latency of the chronic group was longer than that of the control group. In spatial probe tests, compared with the control group, the number of times passing over hidden platform decreased in the chronic stress group, the swimming distance through the quadrant of hidden platform and the whole distance were shortened. The chronic stress group significantly decreased levels of IL-1βand IL-2 in blood serum. The chronic stress group significantly increased levels of ACTH and CORT in blood serum.5-HT expressions in brain decreased in chronic stress group. Moreover, Pearson correlation analysis results showed that the levels of IL-1βand IL-2 were negatively correlated with the levels of ACTH and CORT. Path analysis results showed that total scores was positively correlated with the levels of IL-1βand IL-2. Staying time and escape latency were negatively correlated with the levels of IL-2. The level of CORT were positively correlated with staying time and escape latency, and negatively correlated with total scores.
[Conclusion] It was showed that chronic stress could result in anxiety and depression, and suppression of learning and memory, and behavior changes. Chronic stress could suppress the weight and immunological function. Chronic stress may activate the function of HPA. The correlation of behavior and immunity indicate that the behavior may participate in the immunoloregulation.
[方法]选取健康成年的SD大鼠20只,雌雄各半,随机分为正常对照组和慢性应激组,每组10只。采用4种应激方式建立慢性应激动物模型。在应激过程中每周检测动物的体重及旷场实验得分。1.应激结束后,采用旷场实验、悬尾实验以及Morris水迷宫实验检测大鼠心理行为及学习记忆能力的变化；2.断头处死后取血清采用ELISA方法检测IL-1β、IL-2水平,采用放射免疫方法检测ACTH、CORT的含量；3.取脑组织切片采用免疫组织化学ABC法检测5-HT的表达。
[结果]1.大鼠体重及行为学测试：1)两组雄性大鼠的体重均随时间的增加而增加,但慢性应激组大鼠第2、3、4、5周末体重均低于对照组(P<0.05)。两组雌性大鼠体重也随时间的增加而增加,第5周末应激组大鼠的体重低于对照组(P<0.05)；2)慢性应激组大鼠旷场实验水平得分、垂直得分和总分均随时间呈下降趋势。与正常对照组相比,慢性应激组大鼠第3、4、5周末水平得分、垂直得分和总分均降低(P<0.05)。与正常对照组相比,慢性应激组大鼠中央格停留时间随时间呈上升趋势,且第3、4、5周末中央格停留时间延长(P<0.05)；3)悬尾实验中,慢性应激组大鼠的不动时间延长(P<0.01)；4)4天的Morris水迷宫定位航行实验中,两组大鼠的平均潜伏期(LT)均呈下降趋势,但与正常对照组相比,慢性应激组大鼠从第二天开始,LT均延长(P<0.05)。在空间搜索实验中,与正常对照组相比,慢性应激组大鼠穿越原平台的次数减少,原平台象限的游泳距离及游泳总距离明显缩短(P<0.05)。
2.慢性心理应激对大鼠神经内分泌免疫的影响：1)慢性应激组大鼠血清IL-1p、IL-2的含量均低于正常对照组(P<0.01)。慢性应激组大鼠胸腺指数和脾脏指数与正常对照组相比差异无统计学意义(P>0.05)；2)与对正常照组相比,慢性应激组大鼠血清CORT、ACTH的含量均升高(P<0.01)。慢性应激后雄性大鼠血清ACTH含量比雌性大鼠高(P<0.05)；3)与正常对照组相比,慢性应激组大鼠海马锥体细胞间隙增大,排列疏松不齐,5-HT表达减少。4)Pearson相关分析显示慢性应激时大鼠血清IL-1p、IL-2的含量与血清CORT、ACTH的含量呈负相关。
3.通径分析结果显示大鼠血清IL-1p的含量与旷场实验总分呈正相关；IL-2的含量与LT、不动时间呈负相关,与旷场实验总分呈正相关；CORT的含量与LT、不动时间呈正相关,与旷场总分呈负相关。
[结论]慢性心理应激在心理行为方面可以导致机体焦虑、抑郁、行为异常、以及学习记忆能力的减退；在生理方面抑制体重的增长,降低大鼠血清IL-1β、IL-2的水平,升高血清ACTH、CORT水平,激活HPA轴,引起HPA轴功能亢进,可能导致机体免疫力下降,引发心身疾病。心理行为与内分泌免疫之间的相互关系,提示慢性心理应激时机体免疫内分泌与心理行为之间存在相互调节和相互作用。
[Objective] To study the effects of chronic psychological stress on behaviors, and learning and memory abilities, and immunological function, and neuroendocrine function, and to improve the important and scientific basis for intervention in sub-health.
[Methods] 20 SD rats, adult and health, were randomly divided into control group and chronic stress group(n=10 in each group).The rat mode of stress was made by different multi-stress,4 weeks running. After stress, the Open-field test, Morris water maze test and suspend tail test were performed to test the change of mood and behaviors, and learning and memory abilities of rats. After the experiment, thymus index and spleen index were measured. ELISA was applied to measure levels of interleukine-1β(IL-1β) and interleukine-2(IL-2) in blood serum. RIA was applied to measure levels of ACTH and CORT in blood serum. Expression of 5-HT in neural cells in rats'brain tissue were measured with ABC of immunohistoc-hemical method.
[Results] Chronic stress significantly suppressed body weight gain. The increases of body weight in the chronic group were significantly lower than that in the control group. Compared with the control group, the chronic stress group had relatively fewer crossing scores, and rearing scores, and total scores. In suspend tail test, the chronic group had relatively longer staying time. In hidden-platform training of Morris water maze, the mean escape latency of the chronic group was longer than that of the control group. In spatial probe tests, compared with the control group, the number of times passing over hidden platform decreased in the chronic stress group, the swimming distance through the quadrant of hidden platform and the whole distance were shortened. The chronic stress group significantly decreased levels of IL-1βand IL-2 in blood serum. The chronic stress group significantly increased levels of ACTH and CORT in blood serum.5-HT expressions in brain decreased in chronic stress group. Moreover, Pearson correlation analysis results showed that the levels of IL-1βand IL-2 were negatively correlated with the levels of ACTH and CORT. Path analysis results showed that total scores was positively correlated with the levels of IL-1βand IL-2. Staying time and escape latency were negatively correlated with the levels of IL-2. The level of CORT were positively correlated with staying time and escape latency, and negatively correlated with total scores.
[Conclusion] It was showed that chronic stress could result in anxiety and depression, and suppression of learning and memory, and behavior changes. Chronic stress could suppress the weight and immunological function. Chronic stress may activate the function of HPA. The correlation of behavior and immunity indicate that the behavior may participate in the immunoloregulation.
引文
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