臺灣博碩士論文加值系統

腦出血(Intracerebral hemorrhage)造成病人高死亡率及殘疾，而腦出血的患者若合併高血糖則會有更為嚴重的臨床病徵及較差的神經功能，所以本研究利用蛋白質體學來探討高血糖在腦出血所扮演的角色，我們利用腹腔注射鏈佐黴素(streptozotocin)來誘導大鼠高血糖之形成；腦出血動物模式則利用腦立體定位儀在右側紋狀體注射膠原蛋白酶(collagenase)及肝素(heparin)。實驗結果發現高血糖組(n=6)的出血面積明顯大於其他組別。誘導腦出血後第一天高血糖組雙臂握力測試的結果明顯的低於正常血糖組。利用二維電泳(2-DE)及質譜儀(MS)檢測高血糖組及正常血糖組大鼠腦出血周邊組織的蛋白質體表現，結果顯示有八個蛋白質被鑑定出來。值得一提的是腦出血的組別中，正常血糖組的白蛋白(albumin)的表現有增加，但高血糖組的卻沒有。巧合的是，在高血糖組別中觀察到出血組織周圍的神經細胞有顯著細胞凋亡(apoptosis)的現象。以上結果說明在急性腦出血的過程中，白蛋白扮演保護的功能,且會被不同的血糖濃度所決定。
本研究可能未來對出血性腦血管疾病的藥物開發相關研究有所貢獻。

Intracerebral hemorrhage (ICH) is associated with high mortality and disability, and hyperglycemia worsens the clinical and neurological outcomes of patients with ICH. In this study, we utilized proteomic approaches to investigate the role of hyperglycemia in ICH. Hyperglycemia was induced by intraperitoneal injection of streptozotocin (STZ) in adult Sprague–Dawley male rats; ICH was induced by stereotaxic infusion of collagenase/heparin into the right striatum. It was observed that the size of induced hemorrhage was significantly larger in the hyperglycemic group (n =6 in each group). On the first day after ICH, an apparent decrease in the bilateral grasp was also observed for the lesioned hyperglycemic rats compared with normoglycemic ones. When employing 2-DE and MS to examine the proteomes of perihematomal and control regions in individual hyperglycemic and normoglycemic rats, eight differentially expressed protein targets were identified. Most noteworthy, in response to ICH significant increase of albumin was ubiquitously observed in the brains of normoglycemic rats but not in the brains of hyperglycemic rats. Coincidentally, more significant neuronal apoptosis were found in the perihematomal regions of hyperglycemic rats. These observations described suggest the protection role of albumin in acute stage of ICH, which may be dependent on different blood sugar levels.
Furthermore, the present research provides new ideas for the further searching for a medication on the cerebrovascular diseases.

正文目錄頁
正文目錄...........................................................................I
『表』目錄......................................................................II
『圖』目錄......................................................................III
中文摘要..........................................................................IV
英文摘要...........................................................................V


正文:
源起................................................................................1
緒言................................................................................3
材料與方法....................................................................5
結果................................................................................16
討論................................................................................35
結論................................................................................40
參考文獻........................................................................41

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