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系統識別號 U0026-1807201714022800
論文名稱(中文) 探討 Lovastatin對於創傷性腦損傷的治療效果及其機轉
論文名稱(英文) Investigation of the beneficial effects of lovastatin on traumatic brain injury
校院名稱 成功大學
系所名稱(中) 藥理學研究所
系所名稱(英) Department of Pharmacology
學年度 105
學期 2
出版年 106
研究生(中文) 蔡立宸
研究生(英文) Li-Chen Tsai
學號 S26041062
學位類別 碩士
語文別 英文
論文頁數 87頁
口試委員 指導教授-簡伯武
口試委員-蕭雅心
口試委員-陳柏熹
口試委員-林惠菁
中文關鍵字 創傷性腦損傷  憂鬱症  AMPK  Lovastatin 
英文關鍵字 Traumatic brain injury  Depression  AMPK  Lovastatin 
學科別分類
中文摘要 創傷性腦損傷是發展國家中常見的死因及造成後天傷殘的原因。目前並未有藥物能有效治療創傷性腦損傷,因此開發相關治療方式仍然是必須的。在本實驗中我們發現相較於無腦傷大鼠,腦損傷大鼠出現較明顯憂鬱以及焦慮傾向。我們也發現在腦損傷大鼠海馬體的齒狀回中,有較高的FJC陽性細胞數、梗塞體積、膠質原纖維酸性蛋白(GFAP)及腫瘤壞死因子α(TNF-α)。而給予預處理降血脂藥物lovastatin可以有效改善這些因腦損傷而引起的不良結果。同時我們發現lovastatin預處理可以活化腦損傷大鼠海馬體的齒狀回中LKB1/AMPK訊號路徑,推測lovastatin可能透過AMPK這條訊息傳遞路徑來達到抗發炎並減輕腦損傷的影響。因此藉由AMPK抑制劑 Compound C來抵消lovastatin活化AMPK的能力,發現lovastatin改善腦損傷的能力因而消失。從以上的實驗結果我們推論,預處理lovastatin改善因腦損傷而引起的憂鬱行為及焦慮行為的能力,可能是經由調節AMPK這條訊息傳遞路徑而來。
英文摘要 Traumatic brain injury (TBI) is a common cause of death and acquired disability in the developing and developed countries. Currently, no drug has been proved effective enough to treat TBI, therefore, treatment of TBI remains necessary. Here we found lovastatin pretreatment had beneficial effects on TBI rats. TBI rats displayed depression-like and anxiety-like behavior compared to sham-operated rats. TBI rats also exhibited significantly higher level of Fluoro-Jade® C positive cells, infarct volume, Glial fibrillary acidic protein (GFAP) and tumor necrosis factor alpha (TNFα) as compared to sham-operated rats in hippocampal dentate gyrus. Pretreatment of lovastatin significantly improved these adverse effects of TBI. However, the beneficial effects of lovastatin pretreatment were blocked by AMPK inhibitor, Compound C. Taken together, these results demonstrate that lovastatin pretreatment ameliorates fluid percussion-induced brain injury, depression and anxiety and these effects are likely mediated by AMPK signal.
論文目次 中文摘要 Abstract in Chinese....................1
英文摘要 Abstract in English....................3
Acknowledgement................................5
Content........................................6
圖表索引 Lists of Figures and Tables............7
縮寫檢索表 Abbreviations........................10
Introduction...................................12
Specific Aims..................................29
Materials and Methods..........................31
Results........................................46
Discussion.....................................58
References.....................................63
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