發(fā)布時間：2018-06-26 00:42

  本文選題：抑郁 + 應激��； 參考：《陜西師范大學》2013年碩士論文

【摘要】：抑郁癥是一種高發(fā)病率、高死亡率及高復發(fā)率的情感障礙性精神疾病。慢性應激是引起抑郁癥發(fā)生的一個關鍵因素。在現(xiàn)代社會,生活節(jié)奏不斷加快,人們面臨的各種生活、社會壓力不斷增加,致使抑郁癥的發(fā)病也呈逐年上升的趨勢,這給人們生活以及國家經(jīng)濟發(fā)展帶來極大的負擔。據(jù)世界衛(wèi)生組織預測,到2030年,抑郁癥可能成為全球負擔最大的疾病。 關于抑郁癥的發(fā)病機制,主要從神經(jīng)遞質與受體失調、神經(jīng)可塑性等方面研究較多。而近年來神經(jīng)免疫在抑郁癥發(fā)生中的作用越來越引起人們的關注。轉化生長因子-β1(Transforming growth factor-beta1, TGF-β1)不僅在控制炎癥、免疫反應以及組織損傷中發(fā)揮重要作用,且通過多種途徑對神經(jīng)發(fā)揮保護作用。研究發(fā)現(xiàn),抑郁癥中TGF-β1表達異常。硒蛋白P (Selenoprotein P, SelP)對硒轉運及維持體內硒平衡,維持正常腦功能非常重要。硒蛋白P與一些神經(jīng)退行性疾病有關。硒蛋白P基因敲除導致神經(jīng)損傷,突觸可塑性改變,由此引起空間學習記憶以及運動協(xié)調能力的改變。一氧化氮(nitricoxide, NO)過多導致神經(jīng)損傷從而引發(fā)抑郁,iNOS拮抗劑具有抗抑郁效應。有研究表明,TGF-β1抑制硒蛋白P的表達,且TGF-β1通過下調iNOS表達負性調控NO的產(chǎn)生。這些研究結果提示,抑郁發(fā)生與TGF-β1、硒蛋白P和NO是有關系的。海馬結構和功能的改變與抑郁癥的發(fā)生密切相關,然而,在應激性抑郁發(fā)生中,海馬內TGF-β1、硒蛋白P和NO的變化、作用及其相互關系并不清楚,也沒有系統(tǒng)的研究和報道。 因此,本實驗通過建立慢性不可預見性溫和應激(chronic unpredictable mild stress, CUMS)抑郁模型,海馬內微量注射TGF-β1以及TGF-βⅠ型受體激酶抑制劑LY-364947,測量體重變化率,運用糖水消耗實驗、曠場實驗以及懸尾實驗檢測大鼠行為變化,并采用免疫組織化學、酶聯(lián)免疫吸附(ELISA)和western blot方法檢測大鼠海馬內TGF-β1和硒蛋白P的變化,硝酸還原試劑盒檢測NO含量的變化,試圖探討慢性不可預見性溫和應激中TGF-β1的作用及其與硒蛋白P、NO的關系。實驗結果如下： 1、與正常對照組相比,CUMS大鼠表現(xiàn)出明顯的抑郁樣行為；應激導致海馬內TGF-β1含量顯著升高,硒蛋白P表達顯著下降。 2、正常大鼠海馬內注射TGF-β1并不導致抑郁樣行為,相反,CUMS同時海馬內注射TGF-β1明顯改善應激誘導的抑郁樣行為；正常和CUMS大鼠海馬注射TGF-β1,均能明顯抑制硒蛋白P的表達。 3、應激的同時注射LY-364947阻斷TGF-β1信號通路同樣具有抗抑郁效應,此時硒蛋白P表達較CUMS組明顯升高。 4、各組內NO的含量沒有顯著性變化。 以上結果表明海馬TGF-β1與硒蛋白P參與了慢性應激反應,硒蛋白P對海馬可能具有保護作用。TGF-β1可能通過TGF-βⅠ型受體抑制硒蛋白P的表達參與抑郁癥的發(fā)生,而TGF-β1的抗抑郁作用可能是經(jīng)過TGF-βⅠ型受體以外的其它途徑實現(xiàn)的。降低NO的含量可能不是TGF-β1及硒蛋白P發(fā)揮作用的關鍵。
[Abstract]:Depression is a kind of emotional disorder with high morbidity, high mortality and high recurrence rate. Chronic stress is a key factor causing depression. In modern society, the rhythm of life is accelerating, people are facing all kinds of life, and social pressure is increasing, which causes the trend of depression to increase year by year. People's lives and the economic development of the country pose a great burden. According to WHO, by 2030, depression may become the biggest burden in the world.
The pathogenesis of depression is mainly from neurotransmitters and receptor disorders, neuroplasticity and other aspects. In recent years, the role of neuroimmunology in the development of depression has attracted more and more attention. Transforming growth factor - beta 1 (Transforming growth factor-beta1, TGF- beta 1) is not only in control of inflammation, immune response and group. It is important to play an important role in the damage to the nerve. It is found that the expression of TGF- beta 1 is abnormal in depression. Selenoprotein P (Selenoprotein P, SelP) is very important for selenium transport and maintenance of selenium balance in the body and maintenance of normal brain function. Selenoprotein P is related to some neurodegenerative diseases. Selenoprotein P knockout It causes nerve damage, synaptic plasticity changes, resulting in changes in spatial learning and memory and movement coordination. Nitric oxide (nitricoxide, NO) leads to nerve damage and causes depression, and iNOS antagonists have antidepressant effects. Studies have shown that TGF- beta 1 inhibits the expression of selenoprotein P, and TGF- beta 1 reduces the negative expression of iNOS by downregulating the expression of iNOS Regulation of the production of NO. These findings suggest that depression is related to TGF- beta 1, selenoprotein P and NO. Changes in the structure and function of the hippocampus are closely related to the occurrence of depression. However, in the occurrence of stress depression, the changes in the TGF- beta 1, selenoprotein P and NO in the hippocampus are not clear, and there is no systematic study. And reports.
Therefore, by establishing a chronic unpredictable mild stress (chronic unpredictable mild stress, CUMS) depression model, microinjection of TGF- beta 1 in the hippocampus and LY-364947 of the TGF- beta kinase inhibitor kinase inhibitor, the rate of body weight change was measured, and the behavior changes of rats were detected by using sugar water consumption experiment, open field experiment and tail suspension test. The changes of TGF- beta 1 and selenoprotein P in the hippocampus of rats were detected by immunohistochemistry, enzyme linked immunosorbent assay (ELISA) and Western blot, and the changes of NO content were detected by the nitrate reduction kit. The effects of TGF- beta 1 on chronic unpredictable mild stress and the relationship with the selenium protein P and NO were investigated. The experimental results were as follows:
1, compared with the normal control group, CUMS rats showed significant depressive behavior. Stress resulted in a significant increase in the TGF- beta 1 content in the hippocampus and a significant decrease in selenoprotein P expression.
2, injection of TGF- beta 1 in the hippocampus of normal rats did not lead to depressive like behavior. On the contrary, CUMS injection of TGF- beta 1 in the hippocampus significantly improved the depressive behavior induced by stress, and TGF- beta 1 in the hippocampus of normal and CUMS rats could significantly inhibit the expression of selenoprotein P.
3, the simultaneous injection of LY-364947 and TGF- beta 1 signaling pathway also had antidepressant effect. The expression of selenoprotein P was significantly higher than that in CUMS group.
4, there was no significant change in the content of NO in each group.
The above results show that hippocampal TGF- beta 1 and selenoprotein P participate in chronic stress response. Selenoprotein P may have protective effect on hippocampus.TGF- beta 1 may participate in the occurrence of depression by inhibiting the expression of selenoprotein P by TGF- beta type I receptor, and the antidepressant effect of TGF- beta 1 may be achieved through other pathways other than TGF- beta type I receptor. Low NO content may not be the key to TGF- beta 1 and selenoprotein P.
【學位授予單位】：陜西師范大學
【學位級別】：碩士
【學位授予年份】：2013
【分類號】：R749.4

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