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博碩士論文 etd-0914116-091519 詳細資訊
Title page for etd-0914116-091519
論文名稱
Title
第一型乙型轉化生長因子在海洋胜肽對於神經病變性大白鼠之止痛作用中的角色
The role of spinal transforming growth factor-beta 1 in the anti-nociceptive effects of a marine-derived peptide in neuropathic rats
系所名稱
Department
畢業學年期
Year, semester
語文別
Language
學位類別
Degree
頁數
Number of pages
163
研究生
Author
指導教授
Advisor
召集委員
Convenor
口試委員
Advisory Committee
口試日期
Date of Exam
2016-06-16
繳交日期
Date of Submission
2016-10-14
關鍵字
Keywords
神經病變性疼痛、海洋胜肽、磷酸二酯酶4D、慢性縮窄性損傷、發炎性介質
marine-derived peptides, PDE4D, chronic constriction injury, neuropathic pain, inflammatory cytokines
統計
Statistics
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The thesis/dissertation has been browsed 5675 times, has been downloaded 0 times.
中文摘要
神經病變性疼痛是由於損壞周圍神經或中樞神經系統(central nervous system, CNS)的結果,通常難以治癒,其特徵包括熱痛覺過敏以及觸覺痛敏等。目前臨床藥物仍無法有效減緩所有神經病變性疼痛之症狀,因此,仍需要探索治療神經病變性疼痛的新型藥物。坐骨神經之慢性縮窄性損傷(chronic constriction injury, CCI)是常用的神經病變性疼痛動物模型。中樞神經系統內,微膠細胞(microglia)和星狀細胞(astrocyte)在疼痛扮演重要的角色,會藉由釋放發炎性介質,而促進疼痛的形成與維持。本研究表明,海洋胜肽MSP-3對於慢性縮窄性損傷大鼠顯著地產生鎮痛作用。另一方面,MSP-3也能預防慢性縮窄性損傷大鼠之疼痛行為的形成,其中也伴隨著脊髓之神經發炎性疼痛的降低。同時,MSP-3也未引起正常大鼠產生外觀或行為的異常。另外,合併給予抑制劑,以評估MSP-3可能作用之分子機轉,綜合以上研究結果,顯示海洋胜肽MSP-3有極高潛力,可以應用於減緩神經病變性疼痛,且其可能是經由磷酸二酯酶4D(phosphodiesterase 4D, PDE4D)的增量表現而產生鎮痛作用。
Abstract
Neuropathic pain occurs as a consequence of damage to peripheral nerves or the central nervous system (CNS) and is often refractory to cure. At present, clinical drugs have not been to alleviate symptoms of neuropathic pain, so it still need to explore novel drug for neuropathic pain. Chronic constriction injury (CCI) is a commonly used neuropathic animal model. In neuropathic animal models, glial cells in the CNS plays a important role, specifically microglia and astrocyte, are reported to promote the formation and maintenance of pain by releasing inflammatory cytokines. In the present study, marine-derived peptides MSP-3 generates significant analgesic effect in CCI-induced rats. On the other hand, MSP-3 significantly prevent pain in a rat CCI model for neuropathic pain and attenuate neuroinflammation. MSP-3 also do not cause abnormal of appearance or behavior in normal rats. In addition, the combined of inhibitor and MSP-3 assess the possible of the MSP-3 molecule mechanisms. Base on our findings, marine-derived peptides MSP-3 displays high potential for drug development to attenuate neuropathic pain and is analgesic effect by upregulation of phosphodiesterase 4D (PDE4D).
目次 Table of Contents
論文審定書 i
致謝 ii
摘要 iii
Abstract iv
目錄 v
圖目錄 vii
表目錄 xii
中英文對照及縮寫表 xiii
第一章、前言 1
疼痛背景 1
神經病變性疼痛的發生 2
神經膠質細胞在神經病變性疼痛上之角色 5
現行止痛藥物的類型 11
現行神經病變性疼痛藥物的概述 15
海洋藥物的開發現狀與不足 17
抗微生物胜肽的發現與機轉 24
研究的動機與目的 31
第二章、實驗材料與方法 32
實驗動物 32
椎管手術 32
坐骨神經結紮誘發神經病變性疼痛模式 33
疼痛程度評估 33
樣本組織收集及冷凍切片分析 34
組織免疫化學螢光染色 35
使用的目標抗體 36
免疫化學螢光染色定量 36
實驗動物之分組 37
數據分析 38
第三章、結果 39
第四章、討論 120
MSP-3抑制CCI所導致疼痛行為 120
椎管給予MSP-3預防CCI大鼠疼痛的形成 122
椎管給予MSP-3可減輕CCI大鼠的脊髓背角之神經發炎情形 122
MSP-3抑制神經病變性疼痛之作用探討 124
阻斷PDE4D路徑對於神經發炎之影響 128
MSP-3未來展望 130
參考文獻 131
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