臺灣博碩士論文加值系統

憂鬱症是現代社會常見的精神疾病，除了帶來病患失能或是死亡的風險，對於病患家人以及社會更是沈重的負擔，世界衛生組織預測，在 2030 年憂鬱症將會攀升至全球負擔性疾病首位。臨床證據顯示當體內處於發炎狀態時，憂鬱症的發生率顯著較高，而憂鬱症病患血液中促發炎細胞激素也有提升的現象。目前憂鬱症最主要透過抗憂鬱藥物的治療為主，許多研究都證實抗憂鬱藥物具有良好的功效，但在臨床應用上卻因其副作用而導致病患的順應性低下，因此，發展憂鬱症的預防及替代療法當前迫切需要的課題。茯苓（Poria cocos Schw. Wolf） ，是一種多孔菌科乾燥真菌的菌核。最初記載於本草經，味甘、性平，具有養心安神、益脾和胃、利水滲濕之功效，已有千年的食用歷史。現代醫學研究顯示，茯苓具有抗腫瘤、抗發炎及抗氧化等的功效。因此，本實驗欲利用強迫游泳試驗及不可預期慢性輕度壓力等急、慢性動物模式誘導大鼠產生類憂鬱傾向，並觀察介入不同劑量之茯苓水萃物是否具有抗憂鬱的效果。結果顯示，茯苓水萃物能顯著減少大鼠的不泳動時間，且給予茯苓水萃物 300 mg/kg bw 之組別能藉由減少血清素代謝速率改善動物類憂鬱症狀，以及因壓力而造成蔗糖偏好下降以及探索能力下降的現象，與負控制組相比，能顯著提升蔗糖偏好程度約 26% 及探索能力約 55%。此外，壓力會造成 p38 MAPK（p38 Mitogen-activated protein kinases）蛋白磷酸化比例上升，會進一步啟動下游轉錄因子 NF-κB（nuclear factor kappaB）之訊息傳遞而產生大量促發炎細胞激素腫瘤壞死因子-α（tumor neucrosis factor alpha, TNF-α）。由以上結果推測，茯苓水萃物於強迫游泳試驗中可以藉由降低血清素代謝速率約 44% 達到抗憂鬱的效果，並於不可預期慢性輕度壓力試驗中藉由減少 p38 MAPK 相關蛋白路徑表現量約 34-42%，降低大鼠發炎反應，達到抗憂鬱的功效，由此可見茯苓於預防甚至輔助治療憂鬱症，甚至在未來開發成為菇類抗憂鬱的保健產品皆具有相當高的潛力。

Depression is a chronic illness that significantly affects a person’s moods, behaviour and general health. Predicted to be the first contribution of global burden disease in 2030 according to WHO. Inflammation is a protective response of the human body to various harmful stimuli including physical trauma, noxious chemicals, and microbiologic agents. However, chronic inflammation can lead to serious tissue damage and inflammation-associated diseases, like depression. At present, there are several classes of classical antidepressants in clinical practice. However, most of these drugs are undesirable, due to their side effects and efficacy for only a certain proportion of patients. Thus, there is an unmet need for safe, well‐tolerated and powerful antidepressants. Poria cocos Wolf, commonly known as ‘Fu-Ling’, is a medicinal fungus and it is widely distributed in Korea, China, and East Asian countries. This fungus has long been utilized as a traditional medicine for its sedative, diuretic, and tonic effects. Recently, the sclerotia of Poria cocos were shown to have many biological activities including anticancer, anti-inflammatory, antioxidant and stabilize the mind. Therefore the main purpose of the current study was to verify whether water extract of Poria cocos conferred an antidepressant-like effect on the depressive mouse model established by forced swim test and unpredictable chronic mild stress, then explore its possible mechanism. The results shown that Poria cocos may decrease the immobility time. And the depression-related behaviors including sucrose preference test and open field test, indicated that water extract of Poria cocos 300 mg/kg can improve the depression symptoms. Western blot analysis displayed down-regulated expressions of p38 mitogen-activated protein kinase (MAPK) and decreased the expressions of tumor necrosis factor-alpha (TNF-α). Thus, it was supposed that water extract of Poria cocos might be useful for the treatment of chronic depression possibly through p38 MAPK pathway. In conclusion, we found that water extract of Poria cocos exhibited anti-inflammatory effects on depression prevention.

目錄
中文摘要.......................................................................................................I
英文摘要......................................................................................................II
目錄.............................................................................................................IV
圖次...........................................................................................................VII
表次.............................................................................................................IX
縮寫表..........................................................................................................X
第一章、前言...............................................................................................1
第二章、文獻回顧.......................................................................................2
第一節、憂鬱症................................................................................2
一、憂鬱症簡介......................................................................2
二、憂鬱症分類......................................................................2
三、憂鬱症診斷......................................................................3
四、憂鬱症之盛行率..............................................................4
五、憂鬱症之致病機轉..........................................................8
六、憂鬱症之治療................................................................14
第二節、憂鬱症研究模式..............................................................18
一、動物模式........................................................................18
二、細胞模式........................................................................20
第三節、茯苓..................................................................................21
一、茯苓簡介........................................................................21
二、茯苓之活性成分............................................................22
三、茯苓之生理活性............................................................23
第三章、研究目的及研究假說.................................................................29
第四章、實驗架構.....................................................................................30
第五章、實驗材料與方法.........................................................................31
第一節、實驗材料...........................................................................31
一、茯苓水萃物...........................................................................31
二、實驗藥品...............................................................................31
三、實驗設備與儀器...................................................................32
四、溶液配置………….……………………………...………...34
第二節、實驗方法...........................................................................36
第三節、統計分析方法...................................................................45
第六章、實驗結果.....................................................................................46
第一節、強迫游泳試驗—體重、攝食、飲水量變化...................46
第二節、強迫游泳試驗—開放空間試驗.......................................46
第三節、強迫游泳試驗—不泳動時間...........................................46
第四節、強迫游泳試驗—腦部神經傳導物質含量分析...............46
第五節、不可預期慢性輕度壓力試驗—體重、攝食、飲水量變
化......................................................................................47
第六節、不可預期慢性輕度壓力試驗—蔗糖偏好程度...............47
第七節、不可預期慢性輕度壓力試驗—開放空間試驗...............48
第八節、不可預期慢性輕度壓力試驗—p38 MAPK 相關路徑蛋
白質之表現量..................................................................48
第七章、討論.............................................................................................63
第一節、體重、攝食、飲水量變化之探討...................................63
第二節、開放空間驗結果之探討...................................................64
第三節、強迫游泳試驗結果之探討...............................................65
第四節、腦部神經傳導物質含量及代謝率變化之探討...............65
第五節、不可預期慢性輕度壓力與蔗糖偏好試驗結果之探討...67
第六節、p38 MAPK 相關路徑之探討...........................................68
第八章、結論.............................................................................................71
第九章、未來研究方向.............................................................................73
第十章、參考文獻.....................................................................................74
第十一章、附錄.........................................................................................93

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