臺灣博碩士論文加值系統

在藥物MP與EPO治療對於脊髓損傷的研究中，顯示藥物MP有極大的副作用，雖然對於急性期的脊髓損傷治療有幫助，但長期使用會造成很多後遺症；藥物EPO對於脊髓損傷恢復已有動物實驗證實比藥物MP更好並且它的副作用較少。我們發現脊髓損傷的相關機制仍然有許多不是很清楚，臨床上真正有助於恢復的藥物也尚未找到。故我們希望能全面性地了解脊髓損傷的基本反應機制、分別再進一步地探討藥物MP與EPO對脊髓損傷的反應機制。我們將設計不同的時間點，在時間序列上檢視基因表現量的變化，希望可以區分出藥物MP與EPO對於脊髓損傷反應基因的類型，綜觀這些反應基因群，我們將以生物網絡的方式呈現，提供對於脊髓損傷的反應機制更深入的剖析。

Treatment of spinal cord injury (SCI) has been a frustrating endeavor in neurological medicine because SCI causes a series of devastating damage.

The current treatment of SCI is restricted in the high-dose glucocorticoid drug. The anti-inflammatory therapy, Methylprednisolone (MP), is the currently accepted drug for acute SCI. Anti-inflammatory treatments in experimental studies have been shown to be useful on reducing inflammation and preserving spinal tissues for functional improvement. However, the high-dose MP in acute SCI induced a wide range of side effects in clinical trials, which is normally associated with higher incidence of infectious and metabolic complications in comparison to placebo or other treatments. In addition to MP, recent studies have investigated that Erythropoietin (EPO) can reduce the catastrophe of acute SCI and improve healing process after trauma.

In the present study, we address time series gene expression alteration of spinal cord injury with or without MP or EPO treatment using large oligonucleotide microarray datasets. We illustrated the candidate biological pathways to explain the molecular interactions after treatments such as transcriptional regulation, protein-protein interactions, and phosphorylation. Finally, our analysis revealed significant molecular events of MP/EPO effects and provided potential pharmacological therapeutics that directed to rescue damaged tissue and regeneration in the injured spinal cord.

目 錄
標題 i
審定書 ii
誌謝 iii
目錄 iv
表目錄 v
圖目錄 vi
中文摘要 viii
Abstract xi
第一章 緒論 1
1.1 前言 1
1.2 人類脊髓結構與功能的簡介 2
1.3 脊髓損傷後的影響與改變 6
1.4 中樞神經系統的再生與修復 7
1.5 脊髓損傷的治療 8
1.5.1 甲基類固醇（Methylprednisolone）的介紹 8
1.5.2 紅血球生成素 (Erythropoietin) 的介紹 9
1.6 研究動機與目的 11
第二章 文獻回顧 13
2.1 脊髓損傷的次級傷害機制 13
2.2 藥物MP與EPO用於脊髓損傷治療的動物實驗研究 16
2.2.1 藥物MP用於脊髓損傷治療的動物實驗研究 16
2.2.2 藥物EPO用於脊髓損傷治療的動物實驗研究 21
2.2.3 藥物MP與EPO同時用於治療脊髓損傷的動物實驗研究 30
2.3 脊髓損傷的生物晶片研究 34
第三章 研究方法與材料 40
3.1 脊髓損傷動物實驗設計 40
3.2 脊髓損傷生物晶片實驗設計 42
3.2.1 寡糖核苷酸生物晶片的介紹 42
3.2.2 脊髓損傷的寡糖核苷酸生物晶片實驗 45
3.3 生物晶片實驗資料分析工具 46
3.4 生物晶片實驗資料分析方法 48
3.4.1 資料前置處理方法 49
3.4.2 基因表現量分析方法 52
第四章 研究結果與討論 54
4.1 資料前置處理 54
4.2 基因表現量分析 58
4.2.1 MP與EPO的藥物反應基因群的表現型態 58
4.2.2 時間性MP與EPO藥物反應基因群的生物網絡 64
第五章 參考文獻 72

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