心理應激所致神經(jīng)內(nèi)分泌胸腺軸功能紊亂及中藥調(diào)節(jié)作用研究
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本文關鍵詞:心理應激所致神經(jīng)內(nèi)分泌胸腺軸功能紊亂及中藥調(diào)節(jié)作用研究 出處:《中國中醫(yī)科學院》2006年碩士論文 論文類型:學位論文
更多相關文章: 心理應激 神經(jīng)-內(nèi)分泌-胸腺軸 立早基因 HPA軸 SA軸 加味逍遙丸
【摘要】:心理應激是由于個體在生活適應過程中,因環(huán)境要求與自身應付能力不平衡的認識所引起的一種身心緊張狀態(tài)。近年來,人們越來越關注心理應激造成的身心損害。 本文運用現(xiàn)代研究方法和手段探討了心理應激對神經(jīng)-內(nèi)分泌-胸腺軸功能的影響。通過研究加味逍遙丸對神經(jīng)-內(nèi)分泌-胸腺軸的調(diào)節(jié)來分析其抗心理應激損傷的作用機理。是典型的由方藥探理的中醫(yī)藥現(xiàn)代化研究,具有重要的科學意義和理論價值,具體表現(xiàn)在以下幾個方面。 應用電刺激心理應激箱誘發(fā)心理應激動物模型,用立早基因(c-Fos、c-Jun)二種蛋白為探針,研究了心理應激對中樞神經(jīng)系統(tǒng)即腦功能的影響以及加味逍遙丸的調(diào)節(jié)作用。研究發(fā)現(xiàn)心理應激后1h,四個腦區(qū)(海馬、杏仁核、下丘腦室旁核、下丘腦視上核)c-Fos、c-Jun蛋白開始表達,3h達到高峰,隨即開始下降,其中c-Fos蛋白到應激后6h已回落近正常水平,而c-Jun蛋白在應激后6h仍然維持在相當于應激后1h的水平。我們在同一高峰點做了應激3次及應激5次實驗,c-Fos、c-Jun蛋白的表達仍維持在高峰水平。加味逍遙丸對腦區(qū)立早基因的調(diào)節(jié)是:c-Fos蛋白在用藥第三天杏仁核和下丘腦視上核表達減少,c-Jun蛋白在用藥第三天四個腦區(qū)表達均減少,用藥第五天c-Fos、c-Jun蛋白在四個腦區(qū)表達都明顯減少,說明加味逍遙丸對心理應激小鼠腦區(qū)c-Fos、c-Jun蛋白表達有調(diào)節(jié)作用,可能于用藥第三天起作用。其阻斷下丘腦-垂體-腎上腺皮質(zhì)軸(HPA軸)作用可能與其調(diào)節(jié)下丘腦等核團c-Fos、c-Jun蛋白有關。 用甲吡酮阻斷HPA軸,將加味逍遙丸與其對照研究,觀察血清糖皮質(zhì)激素水平、胸腺細胞凋亡率、胸腺病理改變及細胞免疫功能狀況(NK細胞活性、淋巴細胞轉(zhuǎn)化率)。研究發(fā)現(xiàn)心理應激小鼠表現(xiàn)為HPA軸功能紊亂,對免疫器官的結構和功能產(chǎn)生的影響是:胸腺指數(shù)下降,胸腺細胞凋亡率增加,NK細胞活性、淋巴細胞轉(zhuǎn)化率下降,胸腺組織病理發(fā)生輕度改變;用甲吡酮阻斷HPA軸后,慢性心理應激小鼠血清糖皮質(zhì)激素水平下降,胸腺指數(shù)增加,胸腺細胞凋亡率下降,NK細胞活性增強,淋巴細胞轉(zhuǎn)化率升高,胸腺組織無明顯病理改變。加味逍遙丸的作用與甲吡酮阻斷HPA軸一致,推測加味逍遙丸對胸腺和細胞免疫功能的保護是通過阻斷HPA軸實現(xiàn)的。 用六羥多巴胺(6-oh DA)阻斷交感腎上腺髓質(zhì)軸(SA軸),將加味逍遙丸與其對照研究,觀察指標與甲吡酮阻斷HPA軸相同,結果發(fā)現(xiàn):應激組較對照組胸腺細胞凋亡率顯
[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.
【學位授予單位】:中國中醫(yī)科學院
【學位級別】:碩士
【學位授予年份】:2006
【分類號】:R395;R285
【引證文獻】
相關期刊論文 前1條
1 張曼;張麗萍;劉海鵬;;應激的神經(jīng)-內(nèi)分泌-免疫網(wǎng)絡機制及中醫(yī)藥干預研究進展[J];神經(jīng)解剖學雜志;2008年02期
,本文編號:1369068
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