心理应激所致神经内分泌胸腺轴功能紊乱及中药调节作用研究

发布时间：2018-01-02 11:47

本文关键词：心理应激所致神经内分泌胸腺轴功能紊乱及中药调节作用研究　出处：《中国中医科学院》2006年硕士论文　论文类型：学位论文

【摘要】：心理应激是由于个体在生活适应过程中,因环境要求与自身应付能力不平衡的认识所引起的一种身心紧张状态。近年来,人们越来越关注心理应激造成的身心损害。本文运用现代研究方法和手段探讨了心理应激对神经-内分泌-胸腺轴功能的影响。通过研究加味逍遥丸对神经-内分泌-胸腺轴的调节来分析其抗心理应激损伤的作用机理。是典型的由方药探理的中医药现代化研究,具有重要的科学意义和理论价值,具体表现在以下几个方面。应用电刺激心理应激箱诱发心理应激动物模型,用立早基因(c-Fos、c-Jun)二种蛋白为探针,研究了心理应激对中枢神经系统即脑功能的影响以及加味逍遥丸的调节作用。研究发现心理应激后1h,四个脑区(海马、杏仁核、下丘脑室旁核、下丘脑视上核)c-Fos、c-Jun蛋白开始表达,3h达到高峰,随即开始下降,其中c-Fos蛋白到应激后6h已回落近正常水平,而c-Jun蛋白在应激后6h仍然维持在相当于应激后1h的水平。我们在同一高峰点做了应激3次及应激5次实验,c-Fos、c-Jun蛋白的表达仍维持在高峰水平。加味逍遥丸对脑区立早基因的调节是:c-Fos蛋白在用药第三天杏仁核和下丘脑视上核表达减少,c-Jun蛋白在用药第三天四个脑区表达均减少,用药第五天c-Fos、c-Jun蛋白在四个脑区表达都明显减少,说明加味逍遥丸对心理应激小鼠脑区c-Fos、c-Jun蛋白表达有调节作用,可能于用药第三天起作用。其阻断下丘脑-垂体-肾上腺皮质轴(HPA轴)作用可能与其调节下丘脑等核团c-Fos、c-Jun蛋白有关。用甲吡酮阻断HPA轴,将加味逍遥丸与其对照研究,观察血清糖皮质激素水平、胸腺细胞凋亡率、胸腺病理改变及细胞免疫功能状况(NK细胞活性、淋巴细胞转化率)。研究发现心理应激小鼠表现为HPA轴功能紊乱,对免疫器官的结构和功能产生的影响是:胸腺指数下降,胸腺细胞凋亡率增加,NK细胞活性、淋巴细胞转化率下降,胸腺组织病理发生轻度改变;用甲吡酮阻断HPA轴后,慢性心理应激小鼠血清糖皮质激素水平下降,胸腺指数增加,胸腺细胞凋亡率下降,NK细胞活性增强,淋巴细胞转化率升高,胸腺组织无明显病理改变。加味逍遥丸的作用与甲吡酮阻断HPA轴一致,推测加味逍遥丸对胸腺和细胞免疫功能的保护是通过阻断HPA轴实现的。用六羟多巴胺(6-oh DA)阻断交感肾上腺髓质轴(SA轴),将加味逍遥丸与其对照研究,观察指标与甲吡酮阻断HPA轴相同,结果发现:应激组较对照组胸腺细胞凋亡率显
[Abstract]:Psychological stress is a physical and mental tension caused by the imbalance of cognition between the environmental requirements and self coping ability in the process of life adaptation. In recent years, people pay more and more attention to the physical and mental damage caused by psychological stress.
This paper uses modern research methods to investigate the effect of psychological stress on neuroendocrine function of thymus axis. To analyze the anti psychological stress mechanism through the study of Xiaoyao Pill on regulation of neuroendocrine axis. The thymus was a typical prescription study of modern physical medicine has scientific significance and the important theoretical value, specifically in the following aspects.
The application of electrical stimulation psychological stress box psychological stress induced animal model, with immediate early genes (c-Fos, c-Jun) two protein as a probe of the effect of psychological stress on the brain function of the central nervous system and regulating effect of Modified Xiaoyao Pill. The study found that psychological stress after 1h, four brain regions (hippocampus and amygdala. The paraventricular nucleus, supraoptic nucleus) of c-Fos, c-Jun protein expression peaked at 3h, then began to decline, which c-Fos protein to 6h after stress has dropped to normal levels, and c-Jun protein in 6h after stress remains in the level of 1h after stress. We are in the same peak point the stress and stress 3 times 5 experiments, c-Fos, c-Jun expression remained at the peak level. Regulation of Xiaoyao Pill immediately early gene on brain areas: c-Fos protein in third days of treatment of amygdala and hypothalamic supraoptic nucleus expression decreased, c-Jun protein in Third days of treatment in four brain regions decreased after fifth days, c-Fos, c-Jun protein expression were significantly reduced in four brain regions, indicating that c-Fos Xiaoyao Pill on brain mental stress in mice, the expression of c-Jun protein regulation may play a role in use third days. The occlusion of the hypothalamic pituitary adrenocortical axis (HPA axis) may be related to regulating the hypothalamic nuclei such as c-Fos, c-Jun protein.
Blocking the HPA axis with metyrapone, the Xiaoyao Pill and control study, observation of serum glucocorticoid levels, the rate of apoptosis in thymus, thymic pathology and cellular immune function status (NK cell activity, lymphocyte transformation rate). The study found that psychological stress mice exhibited HPA axis dysfunction, influence the structure and function of immunity the organ is: the thymus index decreased, thymus cell apoptosis, NK cell activity, lymphocyte transformation rate, thymus tissue pathological change slightly; blocking the HPA axis with metyrapone, chronic psychological stress level of glucocorticoid in serum decreased, thymus index increased, thymus cell apoptosis rate decreased, NK increased cell activity, lymphocyte transformation rate increased, no obvious pathological changes of thymus tissue. The effect of Xiaoyao Pill and metyrapone blocking the HPA axis, speculated that Xiaoyao Pill on thymus and cell The protection of the immune function is achieved by blocking the HPA axis.
The sympathetic axis of the adrenal medulla axis (SA axis) was blocked by six hydroxydopamine (6-OH DA). The Modified Xiaoyao Pill and its control were compared with those of the control group. The observed indexes were the same as those of the blockage of HPA axis by methacetin. The results showed that the thymocyte apoptosis rate in the stress group was significantly higher than that in the control group.

【学位授予单位】：中国中医科学院
【学位级别】：硕士
【学位授予年份】：2006
【分类号】：R395;R285

【引证文献】