系統識別號 U0026-0812200911253208
論文名稱(中文) 褪黑激素對腦創傷後STAT活性之影響
論文名稱(英文) Effect of melatonin on the activation of signal transducers and activators of transcription (STAT) after traumatic brain injury
校院名稱 成功大學
系所名稱(中) 生理學研究所
系所名稱(英) Department of Physiology
學年度 93
學期 1
出版年 94
研究生(中文) 陳韋如
研究生(英文) Wei-Ju Chen
學號 S3691407
學位類別 碩士
語文別 中文
論文頁數 86頁
口試委員 口試委員-蘇五洲
中文關鍵字 褪黑激素  腦創傷 
英文關鍵字 melatonin  traumatic brain injury  STAT 
中文摘要 中文摘要
  急性腦創傷會引發氧化壓力和發炎反應進而導致腦組織的受損。先前的研究證實,局部腦缺血模式中產生的活性氧化物質(ROS)和細胞素(cytokine)會直接活化STAT (signal transducers and activators of transcription)蛋白質的成員,STAT1和STAT3。褪黑激素已經被證實在多種神經退化疾病的實驗模式中(包含腦部創傷),藉由抗氧化和抗發炎作用而有效保護神經細胞。然而,褪黑激素對於腦部創傷後STAT活性的影響則尚未被探討。因此,我們使用一定重量的物體以自由落體方式撞擊大鼠腦皮質誘發腦創傷模式,並且建立不同嚴重程度的腦創傷,探討褪黑激素對腦創傷所誘發STATs活性表現的影響。首先,我們的結果證明褪黑激素明顯抑制重度腦創傷所造成皮質和海馬回的神經細胞流失。重度腦部創傷一天後,顯著降低細胞內麩胺基硫的含量和STAT1 及STAT3 DNA結合活性,但顯著增加介白素-6 (IL-6)、誘導型一氧化氮合成酶 (iNOS) 和suppressor of cytokine signaling (SOCS3)的mRNA含量。另外,褪黑激素有效降低重度腦創傷對於創傷周圍皮質所造成IL-6、SOCS3和 iNOS mRNA的表現和回復STAT1 DNA結合活性。但是褪黑激素對於創傷中心皮質所誘發的STAT DNA 結合活性下降及SOCS3 mRNA的增加則無明顯抑制作用。這些結果指出褪黑激素顯著減少腦創傷所造成的傷害並且伴隨著抑制IL-6、iNOS和SOCS3 mRNA的增加以及STAT1 DNA結合活性的下降,至於抑制腦創傷所造成STAT1的活性下降,是否直接參與在褪黑激素的保護作用機制中仍待進一步釐清。
英文摘要 Abstract
  Tissue damage that occurs during and after acute traumatic brain injury (TBI) has been suggested to be attributed to both induction of oxidative stress and inflammation. Previous studies have demonstrated that transcription factors of STAT1 and STAT3, members of signal transducers and activators of transcription (STAT) proteins, are directly activated by reactive oxygen species and participate in the regulation of cytokine-signaling after focal cerebral ischemia. Melatonin has been demonstrated to be able to protect neurons through its anti-oxidative and anti-inflammatory effects in various experimental neuropathologies, including TBI. However, the effect of melatonin on STAT activity during TBI has not been identified yet. In this study, TBI was induced by a controlled weight-drop device on an open cerebral cortex with different percussive depth. First of all, our results demonstrated the melatonin significantiy prevented the neuronal loss induced by severe TBI in hippocampus and cortex. The level of cellular glutathione and DNA binding activity of STAT1 or STAT3 were significantly decreased 1 day after severe TBI. However, mRNA levels of interleukine-6 (IL-6), inducible nitric oxide synthase (iNOS), and suppressor of cytokine signaling (SOCS3) were up-regulated at 1 day after severe TBI. In addition, melatonin could effectively inhibit the increase of IL-6, iNOS, SOCS3 mRNA expression as well as reduction of STAT1 DNA binding activity at penumbra cortex induced by severe TBI. On the contrary, melatonin can not reverse the inhibition of STAT1 DNA binding activity and up-regulation of SOCS3 at core traumatic cortex. These results implicate that the inhibitory effect of melatonin on the reduction STAT1 DNA binding activity and the increase of IL-6, iNOS, and SOCS3 mRNA expression in penumbra cortex may play a role on its ability to reducing TBI injury.
論文目次 目錄
誌謝 ------------------------------------------- 1
目錄 ------------------------------------------- 2
圖目錄 ----------------------------------------- 3
中文摘要 --------------------------------------- 5
英文摘要 --------------------------------------- 7
緒論 ------------------------------------------- 9
材料方法 --------------------------------------- 19
結果 ------------------------------------------- 31
討論 ------------------------------------------- 41
參考資料 --------------------------------------- 52
圖 --------------------------------------------- 62
作者簡介 --------------------------------------- 86
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