Responsive image
博碩士論文 etd-0810104-160600 詳細資訊
Title page for etd-0810104-160600
論文名稱
Title
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
6-hydroxydopamine-induced inflammation in respiratory tract and esophagus of rats and it’s inhibition by free radical scavenger
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
51
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
2004-07-26
繳交日期
Date of Submission
2004-08-10
關鍵字
Keywords
食道、發炎反應、自由基清除劑、呼吸道、六羥基多巴胺
respiratory tract, 6-hydroxydopamine, 6-OHDA, dimethylthiourea, inflammation, DMTU, esophagus
統計
Statistics
本論文已被瀏覽 5688 次,被下載 2101
The thesis/dissertation has been browsed 5688 times, has been downloaded 2101 times.
中文摘要
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。
Abstract
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.
目次 Table of Contents
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
參考文獻 References
Advenier, C., Lagente, V., Boichot, E. 1997. The role of tachykinin receptor antagonists in the prevention of bronchial hyperresponsiveness, airway inflammation and cough. Eur Respir J. 10, 1892-1906.

Barnes, P.J. 2001. Neurogenic inflammation in the airways. Respir Physiol. 125, 145-154.

Boichot, E., Biyah, K., Germain, N., Emonds-Alt, X., Lagente, V., Advenier, C. 1996. Involvement of tachykinin NK1 and NK2 receptors in substance P-induced microvascular leakage hypersensitivity and airway hyperresponsiveness in guinea-pigs. Eur Respir J. 9, 1445-1450.

Chen, S.C., Chang, J.H., Huang H.T. 2004. Digital measurement of edema formation in rat trachea after application of histamine and substance P. Proceeding of 8th Asia- Pacific Conference on Electron Microscopy, Kanazawa, Japan. PP. 900-901

Christian, E.P., Togo, J.A., Naper, K.E., Koschorke, G., taylor, G.A.,Weinreich, D. 1993. A retrograde labeling technique for the functional study of airway-specific visceral afferent neurons. J Neurosci Methods. 47, 147-160

Ellis, J.L., Undem, B.J. 1994. Pharmacology of non-adrenergic, non-cholinergic nerves in airway smooth muscle. Pulm Pharmacol. 7, 205-223.

Furuya, S., Naruse, S., Hayakawa, T. 1998. Intravenous injection of guanylin induces mucus secretion from goblet cells in rat duodenal crypts. Anat Embryol. 197, 359-367

Hsieh, J.H., Chen, R.F., Wu, J.J., Yen, C.T., Chai, C.Y. 1998. Vagal innervation of the gastrointestinal tract arises from dorsal motor nucleus while that of the heart largely from nucleus ambiguus in the cat. J Auton Nerv Syst. 70, 38-50

Huang, H.T. Haskell, A., McDonald, D.M. 1989. Changes in epithelial secretory cells and potentiation of neurogenic inflammation in the trachea of rats with respiratory tract infections. Anat Embryol. 180, 325-341

Huang, H.T. 1993. Unilateral cervical vagotomy decreases the magnitude of neurogenic inflammation induced by capsaicin in the ipsilateral bronchial tree of rats. Anat Embryol. 188, 363-370

Hunter, D.D., Undem, B.J. 1999. Identification and substance P content of vagal afferent neurons innervating the epithelium of the guinea pig trachea. Am J Respir Crit Care Med. 159, 1943-1948.

Jancso, N., Gancso-Gabor, A., Szolcsanyi, J. 1967. Direct evidence for neurogenic inflammation and its prevention by denervation and by pretreatment with capsaicin. Br J Pharmacol. 31, 138-151

Kostrzewa, R.M., Jacobowitz, D.M. 1974. Pharmacological actions of 6-hydroxydopamine. Pharmacol Rev. 26, 199-288

Kummer, W., Fischer, A., Kurkowski, R., Heym, C. 1992. The sensory and sympathetic innervation of guinea-pig lung and trachea as studied by retrograde neuronal tracing and double-labelling immunohistochemistry. Neuroscience. 49, 715-737.

Kuo, H.P., Rohde, J.A., Tokuyama, K., Barnes, P.J., Rogers, D.F. 1990. Capsaicin and sensory neuropeptide stimulation of goblet cell secretion in guinea-pig trachea. J Physiol. 431, 629-641

Levites, Y., Youdim, M.B., Maor, G., Mandel, S. 2002. Attenuation of
6-hydroxydopamine (6-OHDA)-induced nuclear factor-kappaB (NF-kappaB) activation and cell death by tea extracts in neuronal cultures. Biochem Pharmacol. 63, 21-9.

Li, H., Nomura, S., Mizuno, N. 1997. Binding of the isolectin I-B4 from Griffonia simplicifolia to the general visceral afferents in the vagus nerve: a light- and electron-microscope study in the rat. Neurosci Lett. 222, 53-56.

Lin, P .R. (林佩如) 2002. The effect of intravenous administration of 6-hydroxydopamine(6-OHDA) on plasma leakage in rat airways. 國立中山大學碩士論文.

Lin, Y.S., Kou, Y.R. 2000. Acute neurogenic airway plasma exudation and edema induced by inhaled wood smoke in guinea pigs:role of tachykinins and hydroxyl radical. Eur J Pharmacol. 394,139-148.

Lucier, G.E., Egizii, R., Dostrovsky, J.O. 1986. Projection of the internal branch of the superior laryngeal nerve of cat. Brain Res Bull. 16, 713-721

Lundberg, J.M. 1996. Pharmacology of cotransmission in the autonomic nervous system: integrative aspects on amines, neuropeptides, adenosine triphosphate, amino acids and nitric oxide. Pharmacol Rev. 48, 113-178.

Lundberg, J.M., Saria, A. 1983. Capsaicin-induced desensitization of the airway mucosa to cigarette somke,mechanical and chemical irritants. Nature. 302, 251-253

McDonald, D.M. 1988. Neurogenic inflammation in the rat. trachea. I:Changes in venules, leukocytes, and epithelial cells. J Neurocytol. 17, 583-603

Persson, C.G. 1986. Role of plasma exudation in asthmatic airways. Lancet. 2, 1126- 1129.

Persson, C.G. 1988. Plasma exudation and asthma. Lung. 166, 1-23.

Picklo, M.J. 1997. Methods of sympathetic degeneration and alteration. J Auton Nerv Syst. 62, 111-125.

Regoli, D., Boudon, A., Fauchere, J.L. 1994. Receptors and antagonists for substance P and related peptides. Pharmacol Rev. 45, 551-599

Saleh, T.M., Connell, B.J. 1998. The parabrachial nucleus mediates the decreased cardiac baroreflex sensitivity observed following short-term visceral afferent activation. Neuroscience. 87, 135-146.

Solway, J., Leff, A.R. 1991. sensory neuropeptides and airway function. J Appl Physiol. 71, 2077-2087

Sarre, S., Ebinger, G., Michotte, Y. 1996. Levodopa biotransformation in hemi-Parkinson rats:effect of dopamine receptor agonists and antagonists. Eur J Pharmacol. 296, 247-260

Springall, D.R., Cadieux, A., Oliveira, H., Su, H., Royston, D., Polak, J.M. 1987. Retrograde tracing shows that CGRP-immunoreactive nerves of rat trachea and lung originate from vagal and dorsal root ganglia. J Auton Nerv Syst. 20, 155-166.

Sulakvelidze, I., Baluk, P., McDonald, D.M. 1994. Plasma extravasation induced in rat trachea by 6-OHDA is mediated by sensory nerves, not by sympathetic nerved. J Appl Physiol. 76, 701-707

Wang, Y., Wang, S.D., Lin, S.Z., Liu, J.C. 1994.Restoration of dopamine overflow and clearance from the 6-hydroxydopamine lesioned rat striatum reinnervated by fetal mesencephalic grafts. J Pharmacol Exp Ther. 270, 814-21

Weibel, E.S. 1979. Stereological Methods Vol. 1; Practical Methods for Biological Morphometry. Academic Press, London.

Levites, Y., Youdim, M.B., Maor, G., Mandel, S. 2002. Attenuation of 6-hydroxydopamine (6-OHDA)-induced nuclear factor-kappaB (NF-kappaB) activation and cell death by tea extracts in neuronal cultures. Biochem Pharmacol. 63, 21-29

Yoshida, Y., Tanaka, Y., Mitsumasu, T., Hirano, M. Kanaseki, T. 1986. Peripheral course and intramucosal distribution of the laryngeal sensory nerve fibers of cats. Brain Res Bull. 17,95-105
電子全文 Fulltext
本電子全文僅授權使用者為學術研究之目的,進行個人非營利性質之檢索、閱讀、列印。請遵守中華民國著作權法之相關規定,切勿任意重製、散佈、改作、轉貼、播送,以免觸法。
論文使用權限 Thesis access permission:校內外都一年後公開 withheld
開放時間 Available:
校內 Campus: 已公開 available
校外 Off-campus: 已公開 available


紙本論文 Printed copies
紙本論文的公開資訊在102學年度以後相對較為完整。如果需要查詢101學年度以前的紙本論文公開資訊,請聯繫圖資處紙本論文服務櫃台。如有不便之處敬請見諒。
開放時間 available 已公開 available

QR Code