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  • 學位論文

甲基類固醇與紅血球生成素對脊髓損傷的影響:生物晶片資料分析

The influence of Methylprednisolone and Erythropoietin to spinal cord injury:microarray data analysis

指導教授 : 李元綺

摘要


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。

並列摘要


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.

參考文獻


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