臺灣博碩士論文加值系統

「憂鬱症」是盛行率相當高的精神疾病，且被世界衛生組織（WHO）公認與癌症、愛滋病並列為二十一世紀的三大疾病。有許多研究指出類鴉片性胜?（Opiate peptides）與情緒表現有著高度的相關性。本實驗的目的主要探討：內源性腦內啡胜?：腦內啡-2對於具有類似憂鬱症行為小鼠在行為表現（Forced swim test and Tail suspension test）的影響，了解腦內啡-2潛在抗憂鬱的能力，其次，藉由NT2 c1.D1細胞株和SD鼠懷孕18天的胚胎鼠中所取出之初代海馬迴神經細胞，測試細胞存活率與增生能力評估腦內啡-2抗憂鬱的機制。
實驗結果顯示，動物行為模式分析，在管餵灌注第四型雙胜?水解?抑制劑1小時後，腹腔注射腦內啡-2，不論在行為誘導或藥物誘導，均比只有第四型雙胜?水解?抑制劑或腦內啡-2有效降低動物靜止不動時間（p＜0.05）。細胞存活率與增生能力分析，腦內啡-2對於NT2-N或初代海馬迴神經細胞均具有促進細胞存活率與增生能力的影響。由以上實驗結果，推測腦內啡-2在第四型雙胜?水解?抑制劑的輔助下，具有潛在抗憂鬱的能力，可望未來應用在抗憂鬱用藥開發的選擇。

Depression is a recognized major mental health problem. The depression is predicated to be the second main cause of disability in 2020 by the World Healthy Organization. This study was to evaluate antidepressant efficacy of endomorphin-2 on depressive-like animals：behavior-induced（Forced-swim stress）and drug-induced（Reserpine）. In mammalian brain, endomorphin-2 is an endogenous neuropeptides, which is considered as an endogenous ligand for mu-opioid receptors. In this study, we examined the effect of DPP IV inhibitors on endomorhpin-2-induced antidepression. We observed a significant inhibitory effect of p.o. or i.p. administered DPP IV inhibitors on endomorphin- induced behavior in two behavioral models（p＜0.05）. The results of the present study demonstrate that endomorphin-2 produce potent antidepressant-like effects afer i.p. injection in mice.
Our studies using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide（MTS）、bromodeoxyuridine（BrdU）as markers of cell viability and proliferation indicate that Endomorphin-2 treatment enhances proliferation of NT2-N and hippocampus cells. Thus, DPPIV inhibitors coordinating with endomorhphin-2 have a significant anti-depression effects in mice.

中文摘要------------------------1
英文摘要------------------------2
目錄-------------------------3
第一章、緒論----------------------6
第二章、文獻回顧--------------------8
1.憂鬱症（Depression）---------------8
1.1現今診斷方法------------------8
1.2病理機轉-------------------9
2.第四型雙胜?水解?----------------13
2.1 第四型雙胜?水解?抑制劑------------15
3.憂鬱症與DPP IV抑制劑--------------- 16
4.鴉片類神經胜?------------------17
4.1腦內排-------------------18
4.2憂鬱症與腦內啡-2---------------19
5.類似憂鬱症動物行為模式試驗--------------20
5.1強迫游泳試驗----------------21
5.2懸尾試驗------------------21
第三章、 Endomorphin-2潛在抗憂鬱效果探討----------23
一、研究目的----------------------23
二、實驗方法----------------------24
2.1藥品及試劑------------------24
2.2 儀器-------------------25
2.3實驗動物------------------25
2.4 DPP IV抑制劑處理--------------25
2.5第四型雙胜?水解? (DPP IV )分析---------26
2.6 Endomorphin-2於血液與大腦組織之降解分析------27
2.7動物行為模式試驗----------------31
2.8藥物處理與類憂鬱動物模式------------32
2.9 統計分析------------------37
三、結果-----------------------38
3.1 DPP IV抑制劑之劑量探討------------38
3.2 Endomorphin-2於血液與腦組織之降解分析探討-----38
3.3類憂鬱動物模式之行為表現探討-----------39
第四章、 Endomorphin-2對細胞存活率與增生效果探討--42
一、研究目的----------------------42
二、實驗方法----------------------43
2.1藥品及試劑------------------43
2.2 儀器-------------------44
2.3 Endomorphin-2對NT2-N細胞存活率探討-------44
2.4初代海馬迴神經細胞培養--------------49
2.5統計分析------------------51
三、結果-----------------------52
3.1 RA誘導NT2 細胞表現不同神經標記之探討-------52
3.2 Endomorphin-2對於NT2-N細胞之存活率影響------52
3.3 Endomorphin-2對於初代海馬迴神經細胞之存活率影響---53
3.4 Endomorphin-2對於初代海馬迴神經細胞細胞之增生影響--53
第五章、 討論----------------------55
第六章、 結論----------------------59
第七章、 參考文獻--------------------60
第八章、 圖表說明--------------------70
第九章、 附檔----------------------87

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