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研究生:莊豐竹
研究生(外文):Feng-Chu Chuang
論文名稱:六羥基多巴胺誘發大鼠呼吸道及食道之發炎反應及自由基清除劑對其之抑制作用
論文名稱(外文):6-hydroxydopamine-induced inflammation in respiratory tract and esophagus of rats and it’s inhibition by free radical scavenger
指導教授:黃宏圖黃宏圖引用關係
指導教授(外文):hung-tu Huang
學位類別:碩士
校院名稱:國立中山大學
系所名稱:生物科學系研究所
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:2004
畢業學年度:92
語文別:中文
論文頁數:51
中文關鍵詞:食道發炎反應自由基清除劑呼吸道六羥基多巴胺
外文關鍵詞:respiratory tract6-hydroxydopamine6-OHDAdimethylthioureainflammationDMTUesophagus
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迷走神經和脊髓神經的感覺神經纖維,可以調節呼吸道的神經性發炎反應。神經性發炎反應是因為感覺神經末梢受到刺激活化,經由軸突反射使周圍的感覺神經末梢釋放出神經胜肽所導致。神經胜肽包含速激肽類,有substance P、neurokinin A、neurokinin B三種,而大鼠呼吸道的神經性發炎反應主要是藉由SP與小靜脈內皮細胞的NK-1 receptor結合所致,使小靜脈內皮形成內皮隙,血漿從內皮隙漏出到血管之外,蓄積在結締組織造成水腫。
過去的研究顯示,六羥基多巴胺(6-hydroxydopamine, 6-OHDA)也能夠刺激感覺神經引起大鼠氣管的神經性發炎反應。本研究以India ink標定血管滲漏程度,以面積密度表示之,在喉頭、氣管、左支氣管、右支氣管、上食道與下食道,血管滲漏面積密度分別是36.5%、29.5%、27.7%、28.2%、19.2%、15.5%。6-OHDA可以經由非酵素氧化作用形成自由基,而刺激感覺神經元。而使用NK-1 receptor antagonist可以抑制呼吸道的血漿外洩。本實驗測試自由基清除劑的效果,使用全劑量的dimethylthiourea (DMTU) (2.25g/Kg i.v.)前處理15分鐘,以及用較低劑量的DMTU,來研究是否自由基在此反應中扮演重要的角色。藉由India ink整裝封埋組織中,標定的血管面積密度來評估血漿外洩的程度。
本研究發現,以全劑量DMTU前處理可有效抑制神經性發炎反應,在喉頭、氣管、左支氣管、右支氣管、上食道與下食道,分別下降至對照組的12.3%、6.3%、4.8%、8.6%、1.9%、4.8%,故推測6-OHDA是藉由氫氧根自由基刺激感覺神經。同時在不同劑量的DMTU作用之下,發現1/6劑量的DMTU對食道就造成很大的抑制作用,而左、右支氣管則需要到2/3劑量才有明顯的抑制作用,而喉頭與氣管則是隨著DMTU劑量逐漸上升,抑制逐漸增強,顯示呼吸道與食道各部位對DMTU的敏感性並不相同。
Vagal and spinal sensory innervation is responsible for the regulation of neurogenic inflammation in the airways. Neurogenic inflammation is the result of the activation of sensory nerve endings by stimulant and induced through axon reflex to release neuropeptides from sensory nerve endings. These neuropitides are tachykinins, including substance P, neurokinin A and neuronkinin B. Tachykinin-1 (NK-1) receptors are mainly involved in neurogenic inflammation in the airway. It is found that 6-hydroxydopamine (6-OHDA) acts as a stimulant of sensory neurons that produces inflammation in the rat trachea. The magnitude of plasma leakage was expressed by the area density (%) of India ink-labeled blood vessels in tissue whole mounts. The present study found that area density of India ink-labeled blood vessel were 36.5%, 29.5%, 27.7%, 28.2%, 19.2%, 15.5% in the rat larynx, trachea, left bronchus, right bronchus, upper esophagus and distal esophagus after i.v. injection of 6-OHDA (100 mg /Kg), respectively. 6-OHDA could stimulate sensory neurons by free radicals that produced by non-enzymatic oxidation. NK-1 receptor antagonist can inhibit plasma leakage in airways. This study also tested the effect of a free radical scavenger. Rats are pretreated with a full dose (2.25 g/kg, i.v.) or lower doses of dimethylthiourea (DMTU) for a period of 15 min. We found that pretreatment with a full dose of DMTU could inhibit inflammatory plasma leakage induced by 6-OHDA, that was 4.8%, 1.6%, 1.1%, 2.4%, 0.4% and 1.0% in the rat larynx, trachea, left bronchus, right bronchus, upper esophagus and distal esophagus, respectively. It is suggested hydroxyl radicals mediated the inflammatory response in the respiratory tract and esophagus. DMTU dose-dependently decreased 6-OHDA-induced plasma leakage in the rat respiratory tract and esophagus. One sixth dose was effective in inhibition in esophagus. 6-OHDA-induced inflammation in the left and right bronchus could be reduced with 2/3 dose of DMTU. A full dose of DMTU (2.25g/Kg) was needed to inhibit inflammation in the larynx and trachea. It is concluded that sensitivity to 6-OHDA was different in the different part of lower airways and esophagus.
中文摘要…………………………………………………………1
英文摘要..………………………………………………………3
緒言(Introduction)……………………………………………4
研究目的(Purpose of Study)...…………………………….9
材料與方法(Materials and Methods)………………………10
結果(Results)….…………………………………………….17
討論(Discussion)……………………………….……………21
結論(Conclusion)…………………….………….………….26
參考文獻(References)……………………………………….27
圖……………………………………………………………...31
表……………………………………………………………...50
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