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研究生:張瀛双
研究生(外文):Ying-ShuangChang
論文名稱:以valproic acid治療小鼠脊髓損傷之效果評估
論文名稱(外文):Treatment with valproic acid for spinal cord injury in mice
指導教授:許鍾瑜
指導教授(外文):Jung-Yu Hsu
學位類別:碩士
校院名稱:國立成功大學
系所名稱:細胞生物及解剖學研究所
學門:醫藥衛生學門
學類:醫學學類
論文種類:學術論文
論文出版年:2012
畢業學年度:100
語文別:中文
論文頁數:51
中文關鍵詞:脊髓損傷星狀膠細胞
外文關鍵詞:spinal cord injuryastrocytevalproic acid
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  • 下載下載:7
  • 收藏至我的研究室書目清單書目收藏:0
脊髓損傷會造成不同程度的身體機能障礙,例如運動功能的喪失、感覺功能異常以及排尿功能失常等,這些功能的喪失除了對患者本身的生活品質造成影響之外,患者的家庭甚至整個社會都必須付出相當大的代價。遺憾的是,目前尚無有效的藥物來治療受損的脊髓組織以及生理功能。造成脊髓組織無法修復的原因主要是受傷區域中,被活化的星狀膠細胞聚集形成緻密的疤痕組織,它們不僅構成一種物理性的障礙阻擋了神經纖維的再生,更糟的是,星狀膠細胞會分泌抑制神經纖維生長的chondroitin sulfate proteoglycans (CSPGs)而成為一種化學性障礙。因此,減少星狀膠細胞所聚集形成的緻密疤痕組織是脊髓組織復原的關鍵,也是目前藥物開發的目標。目前在臨床上用來治療躁鬱症的藥物Valproic acid被認為具有治療脊髓損傷的潛力,因為Valproic acid是一種 histone deacetylase inhibitor,可調節影響細胞生存或死亡的因子。Valproic acid也具有神經保護與滋養的性質,在其他的研究中,已證實此藥物對退化性神經病變,例如肌萎縮性側索硬化症、阿茲海默症及亨丁頓舞蹈症等等具有療效,更重要的是過去的研究發現Valproic acid可減少星狀膠細胞之內和細胞移動有關的絲狀骨架glial fibrillary acidic protein。然而,目前並不清楚Valproic acid是否真能在脊髓受傷後減少緻密疤痕組織的形成,進而促進神經纖維的再生。因此,我的研究重心在於觀察小鼠脊髓損傷後,給予Valproic acid是否能有效降低受傷區域緻密疤痕組織的形成,進而有較多的神經再生,並評估運動功能及感覺功能是否能因valproic acid的治療而恢復。我的研究成果將使Valproic acid在脊髓組織復原中扮演的角色更為清楚,並對開發脊髓損傷的治療藥物提供一個新的思考方向。
Damaged axons cannot regenerate after spinal cord injury. One major reason for this regenerative failure is the formation of a glial scar. The glial scar, consisting mainly of reactive astrocytes, not only forms a barrier that blocks regenerative axons but also expresses inhibitory molecules chondroitin sulfate proteoglycans (CSPGs) that arrest axon regrowth. Reducing the formation of the glial scar, therefore, is essential for axonal regeneration after spinal cord injury. Valproic acid (VPA) is one candidate that shows such therapeutic potential. As an anti-epileptic drug already in clinical use to treat psychiatric bipolar disorders, VPA can reduce intermediate filaments that affect astrocyte mobility. It also exhibits neuroprotective and neurotrophic properties and has been used to treat several neurodegenerative diseases. To evaluate its therapeutic effect, therefore, I administered VPA subcutaneously to mice after a moderate spinal cord contusion injury at the mid-thoracic level. Immunohistochemistry demonstrated that VPA-treated mice showed a trend toward less GFAP and CGRP immunoreactivity with significant more residual white matter stained by luxol fast blue than the control mice 21 and 42 days after injury. However, the numbers of serotonergic and calcitonin gene-related protein-positive axons were comparable between VPA-treated and control mice. Likewise, both VAP-treated and control mice showed similar extent of functional recovery in a battery of motor and sensory behavior tests at all time points examined. Collectively, my study demonstrates that the effect of VPA treatment appears to be marginal after spinal cord injury. More studies on VPA dosage and treatment time are needed to further evaluate its therapeutic potential to treat spinal cord injury.
中文摘要 ---------- I
英文摘要 ---------- III
誌謝 ------------- IV
目錄 ------------- V
圖目錄 ----------- VI
緒論 ------------- 1
材料與方法 -------- 7
結果 ------------- 18
討論 ------------- 23
結論 ------------- 31
參考文獻 ---------- 32
圖表說明 ----------- 36
附錄 ------------- 50

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