探討天麻水萃物對於慢性誘導類憂鬱大鼠透過促進神經分化生長而具有抗憂鬱效果

Water Extract of Gastrodia elata Bl. May Have Antidepressant Effect via Enhancing Neuroplasticity in Chronic Mild Stress Model

周映妤(YING-YU CHOU)

指導教授 ： 沈立言

國立臺灣大學/生物資源暨農學院/食品科技研究所/碩士(2015年)

https://doi.org/10.6342/NTU.2015.00921

摘要

憂鬱症是一種盛行率高，會造成嚴重失能的精神疾病，世界衛生組織（World Health Organization, WHO）預估憂鬱症將在2030年時成為世界第一的高負擔疾病。此外，憂鬱症患者有比未患病者人高出30倍的自殺風險，WHO在2001年已將其與癌症、愛滋病並列而21世紀三大重要疾病。而台灣的憂鬱症患病率約為9%，並造成約350億台幣的經濟損失，可見憂鬱症的預防與治療是目前迫切需要關注的議題。現行抗憂鬱藥物伴隨許多副作用，進而造成病患順應性減低，加上目前尚未有很好的預防措施，因此替代性中草藥療法或食療預防性方法等，可能可以做為憂鬱症防治策略。本實驗室先前研究發現，天麻水萃物（WGE）在強迫游泳試驗中，可能透過調節神經傳導物質與提升神經可塑性，降低大鼠類憂鬱行為。因此，本研究以慢性壓力模式（CMS），模擬人類長期處於壓力下所造成的神經可塑性下降，使大鼠產生類憂鬱情況來評估WGE之抗憂鬱效果，並進一步以免疫組織染色與西方墨點染色法，探討神經可塑性的表現與相關路徑。行為試驗的結果顯示，慢性壓力組的糖水攝取在第四周較正常組顯著減少，推測此週已誘導類憂鬱行為，而中劑量與低劑量天麻水萃物組分別於第五週和第六週顯著較慢性壓力組增加，推測WGE已有抗憂鬱效果。開放空間試驗（open filed test）中，穿越與站立探索次數是在第四週壓力組顯著低於正常組，WGE中劑量與低劑量組分別於第五、第六週顯著高於與慢性壓力組。免疫組織染色結果顯示在海馬迴部位BrdU細胞存活的表現量中，正常組與天麻水萃物中劑量組均顯著高於慢性壓力組，但在神經細胞增生部分，正常組顯著高於慢性壓力，但天麻水萃物中劑量組與慢性壓力組並沒有顯著差異。另外一個神經可塑性相關蛋白doublecortin（DCX），正常組與中劑量組均顯著多於慢性壓力組，顯示慢性壓力確實可能使神經可塑性下降，給予天麻水萃物中劑量組能夠回復或增加神經可塑性來達到抗憂鬱之效果。由西方墨點驗證海馬迴Slit-1，慢性壓力組顯著高於天麻中劑量組與正常組、額葉皮質則是慢性壓力組顯著高於天麻中劑量組，Slit-2各部位皆沒差異。綜合以上，天麻水萃物可能透過回復神經可塑性來達到抗憂鬱功效，機制可能與抑制Slit-Robo路徑的Slit-1有關。

關鍵字

憂鬱症 ； 慢性壓力模式 ； 神經可塑性 ； 天麻水萃物

並列摘要

According to the World Health Organization（WHO） statistics in 2002, major depressive disorder was defined as one of the three major diseases in 21th century and over 87% suicide victims has mood disorder. In Taiwan, there is over 8.9% population has the depression. Therefore, it is necessary for investigative the pathophysiology of depression and the antidepressant therapeutics. However, depression pathology is multifactorial, which includes monoamine dysregulation, HPA（Hypothalamic–pituitary–adrenal）dysfunction, chronic inflammation and neuroplasticity reduction. The antidepressant used in clinics now brings a lot of side effects. Thus, looking for the alternative therapy and prevention strategy for depression are very important issues. One of animal models used to study depression is the chronic mild stress model .It is a well-known animal model which has high-validity, mimics the real human stressed environment. Recently, Gastrodia elata Blume has shown anxiolytic, mood and memory enhancing effects. In previous study, the water extract of Gastrodia elata Blume (WGE) has antidepressant-like effects in the forced swimming model. Therefore, the aim of this project is to investigate the antidepressant effects of Gastrodia elata Blume in the chronic mild stress model. The results of behavior showed that CMS group markedly decreased in sucrose intake in week 4 comparing to normal group. The group of WGE medium dose and low dose had significantly different with CMS group separately in week 5 and week 6. In the open field test, CMS showed significantly lower than normal and WGE treatment group in crossing in week 4 and week 5. In the rearing part, CMS also had significantly different with normal in week 4 to week 6, even with fluoxetine and L-WGE in week 6. The result of IHC (immunohistochemistry)showed that CMS group was lower number of cell survival and proliferation than normal group. M-WGE showed significantly higher than CMS group in cell survival. In the WGE related antidepressive pathway: Slit-robo, Slit-1 showed that chronic mild stress truly had higher level than normal and WGE treatment in hippocampus. In conclusion, WGE may had antidepressive effect though reverse neuroplasticity in chronic mild stress model.

並列關鍵字

depression ； water extract of Gastrodia elata Blume (WGE) ； chronic mild stress (CMS) ； neuroplasticity

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