本文選題：抑郁癥 + 慢性非預(yù)見(jiàn)性應(yīng)激　； 參考：《華東師范大學(xué)》2008年碩士論文

【摘要】： 抑郁癥作為當(dāng)今世界十大心理疾病之一,越來(lái)越嚴(yán)重地危及到人們的身心健康和正常生活,并成為生物研究的前沿?zé)衢T(mén)課題。本項(xiàng)目通過(guò)建立抑郁癥動(dòng)物模型,探討神經(jīng)肽甘丙肽(Galanin GAL)及其受體在抑郁癥發(fā)生過(guò)程中的作用。 1、模型建立采用慢性非預(yù)見(jiàn)性應(yīng)激(CUMS)和嗅球切除兩種方法建立抑郁癥大鼠模型,運(yùn)用曠場(chǎng)實(shí)驗(yàn)(Open Field),水迷宮及血清皮質(zhì)醇檢測(cè)來(lái)評(píng)價(jià)模型,并通過(guò)高效液相(HPLC)檢測(cè)其各個(gè)腦區(qū)單胺類(lèi)神經(jīng)遞質(zhì)5—羥色胺(5—HT)和去甲腎上腺素(NE)含量的變化。綜合比較了慢性應(yīng)激模型和嗅球切除模型的特點(diǎn)。結(jié)果顯示,兩種模型組大鼠的曠場(chǎng)實(shí)驗(yàn)得分明顯降低,主動(dòng)活動(dòng)能力下降;空間學(xué)習(xí)記憶能力顯著降低,血清皮質(zhì)醇含量顯著升高,慢性應(yīng)激模型組腦內(nèi)神經(jīng)遞質(zhì)含量無(wú)明顯變化,嗅球切除模型組腦內(nèi)神經(jīng)遞質(zhì)含量普遍下降,在特定腦區(qū)變化顯著。 2、腦內(nèi)GAL表達(dá)分析運(yùn)用RT-PCR技術(shù)和熒光定量PCR對(duì)GAL及其受體進(jìn)行定性和半定量檢測(cè)。結(jié)果顯示,慢性應(yīng)激模型組GAL在中縫背核和海馬均上調(diào)。甘丙肽受體1(GalR1)在下丘腦上調(diào),在中縫背核及海馬均下調(diào)。甘丙肽受體2(GalR2)在下丘腦、中縫背核及海馬三個(gè)腦區(qū)均下調(diào)。與熒光定量PCR結(jié)果相吻合。嗅球切除模型組GAL在下丘腦及海馬上調(diào)。GalR1在海馬下調(diào),在下丘腦及中縫背核上調(diào)。GalR2在下丘腦下調(diào),在中縫背核及海馬均上調(diào)。 3、腦室注射甘丙肽及其激動(dòng)劑對(duì)抑郁癥狀的影響動(dòng)物在建立慢性應(yīng)激模型后,進(jìn)行側(cè)腦室埋管手術(shù)。側(cè)腦室慢性注射GAL及GalR2選擇性激動(dòng)劑GAL2-11,觀(guān)察對(duì)抑郁癥狀的影響。側(cè)腦室注射GAL及GAL2-11后,曠場(chǎng)實(shí)驗(yàn)顯示大鼠的主動(dòng)活動(dòng)能力顯著增強(qiáng),空間學(xué)習(xí)能力顯著提高。 結(jié)論慢性非預(yù)見(jiàn)性應(yīng)激和嗅球切除分別模擬了抑郁癥病人外源性和內(nèi)源性的發(fā)病機(jī)制,經(jīng)行為學(xué)和血清皮質(zhì)醇評(píng)價(jià)均為成功的抑郁癥模型。模型建立過(guò)程中GAL及其受體的表達(dá)在不同腦區(qū)出現(xiàn)不同的變化,而側(cè)腦室慢性注射GAL及GalR2激動(dòng)劑GAL2-11可減輕抑郁癥狀,提示GAL很有可能參與了抑郁癥形成過(guò)程中神經(jīng)元功能的調(diào)制。本項(xiàng)目為進(jìn)一步探索在抑郁癥發(fā)生發(fā)展過(guò)程中GAL及其受體與下丘腦、中縫背核和海馬腦區(qū)神經(jīng)元功能下降的相關(guān)性以及抑郁癥發(fā)病的神經(jīng)學(xué)機(jī)制及抗抑郁藥的研制打下基礎(chǔ)。
[Abstract]:Depression, as one of the ten psychological diseases in the world, is more and more seriously endangering people's physical and mental health and normal life, and has become a hot topic in biological research. By creating animal models of depression, To investigate the role of neuropeptide galanin gal and its receptors in the development of depression. 1. Chronic non-predictive stress (CUMS) and olfactory bulb resection were used to establish the rat model of depression. Open field test, water maze and serum cortisol detection were used to evaluate the model. The changes of monoamine neurotransmitters 5-HT and norepinephrine (NE) in various brain regions of the model were detected by high performance liquid chromatography (HPLC). The characteristics of chronic stress model and olfactory bulb resection model were compared. The results showed that the scores of open field test decreased significantly, the ability of active activity decreased, the ability of spatial learning and memory decreased significantly, and the content of serum cortisol increased significantly in both groups. The content of neurotransmitters in brain of chronic stress model group did not change obviously, but the content of neurotransmitter in olfactory bulb resection model group decreased generally. The expression of gal in brain was detected qualitatively and semi-quantitatively by RT-PCR and fluorescence quantitative PCR. The results showed that gal was up-regulated in dorsal raphe nucleus and hippocampus in chronic stress model group. Galanin receptor 1 (GalR1) was up-regulated in hypothalamus, down-regulated in dorsal raphe nucleus and hippocampus. GalR2 was down-regulated in the hypothalamus, dorsal raphe nucleus and hippocampus. The results were consistent with the results of fluorescence quantitative PCR. In olfactory bulb resection model group, gal was up-regulated in hypothalamus and hippocampus. GalR1 was down-regulated in hippocampus and down-regulated in hypothalamus and dorsal raphe nucleus. In the dorsal raphe nucleus and hippocampus. 3. The effect of intraventricular injection of glycine and its agonist on depressive symptoms in rats was performed after chronic stress model was established. The effects of gal and GalR2 selective agonist GAL2-11 on depression were observed. After injection of gal and GAL2-11 into the lateral ventricle, open field experiments showed that the active activity and spatial learning ability of the rats were significantly enhanced. Conclusion chronic non-predictive stress and olfactory bulb resection can simulate the exogenous and endogenous pathogenesis of depression respectively. Both behavioral and serum cortisol evaluation are successful models of depression. The expression of gal and its receptors varied in different brain regions during the establishment of the model. The chronic injection of gal and GalR2 agonist GAL2-11 into the lateral ventricle alleviated the depressive symptoms. It is suggested that gal may be involved in the modulation of neuronal function in the process of depression. This project provides a basis for further exploring the relationship between gal and its receptors and the decrease of neuron function in hypothalamus dorsal raphe nucleus and hippocampal area during the occurrence and development of depression as well as the neuromechanism of depression and the development of antidepressants.
【學(xué)位授予單位】：華東師范大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2008
【分類(lèi)號(hào)】：R-332;R749.4

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