引起大鼠呼吸道發炎反應的因素很多，包括分佈在呼吸道的神經末梢放出的發炎仲介物質，肥胖細胞釋放的組織胺(histamine)，以及細菌感染所釋放的內毒素等等，這些物質所引起的呼吸道炎症反應，包括血漿外洩，黏膜組織皮下水腫，黏液細胞分泌增多等等多種現象，但這些發炎仲介物質在呼吸道的作用機制仍然有未明之處，本次實驗是以靜脈注射的方式，給予高劑量的組織胺誘導大鼠呼吸道的發炎反應，利用印地安墨汁作為追蹤染料，分析不同時間點的血漿外洩程度，此外，我們使用電子顯微鏡技術與組織切片技術，紀錄漿液細胞的分泌活動，以及氣管上皮下方的水腫變化，為了研究組織胺的作用機轉，我們使用了atropine與 mepyramine針對不同的接受器進行拮抗作用，實驗結果顯示注射組織胺五分鐘後，大鼠氣管的黏膜組織就出現了嚴重的血漿外洩，被標定的滲漏血管面積密度為17.24 % ± 2.03 %，比注射生理食鹽水的對照組5.36 % ± 1.11 %高出許多，並且在氣管上皮下方出現明顯的水腫，分佈在氣管上皮的漿液細胞分泌活動也有增多的情形，以mepyramine阻斷組織胺H1接受器會降低以上三種炎症反應，但是以atropine前處理則無法抑制這些發炎現象，根據這些實驗的結果推測組織胺在五分鐘內就可以引發嚴重的發炎反應,並且這些反應主要是透過組織胺H1接受器而引發的。

Many factors influence the inflammatory responses in rat trachea, including inflammatory mediators released from nerve fibers, histamine released by mast cells and endotoxin from the cell walls of bacteria. The inflammatory responses include plasma extravasation, subepithelial edema, and hypersecretion of secretory cells. But the mechanism of inflammation mediated by these factors was not completely understood. In the present study, a high dose of histamine was administered intravenously to induce the inflammation in rat airway. India ink was also injected as a tracer to label the leaky blood vessels in different time points. To investigate the serous cell secretion and subepithelial edema formation, the treacheal tissue was processed for histological study. Electron microcopy was carried out to investigate the ultrastructure of serous cells. To investigate the mechanism of histamine effect, the muscarinic receptor antagonist atropine (1 mg/ml/kg) or histamine H1 receptor antagonist mepyramine (10 mg/ml/kg) was injected 15 min before histamine injection. Five minutes after histamine, plasma leakage and serous cell secretion were extensive. The area density of India ink-labeled leaky vessels was 17.24 % ± 2.03 %. Saline, the vehicle of histamine, produced only a little extravasation. Mepyramine inhibited the histamine-induced plasma extravasation and serous cell degranulation significantly but atropine had no effect. The results suggest that histamine-induced serous cell degranulation is mainly through histamine H1 receptors but not through cholinergic muscarinic receptors in rat trachea.

中文摘要------------------------------------------------------------------------1
Abstract------------------------------------------------------------------------2
緒論------------------------------------------------------------------------------3
研究目的------------------------------------------------------------------------6
材料與方法---------------------------------------------------------------------7
實驗結果------------------------------------------------------------------------13
討論------------------------------------------------------------------------------18
結論------------------------------------------------------------------------------25
參考文獻------------------------------------------------------------------------26
圖表與圖解---------------------------------------------------------------------29

Baluk P. , Nadel J. A. , and McDonald D. M. 1993. Calcitonin gene-related peptide in secretory granules of serous cells in the rat tracheal epithelium. Am. J. Respir. Cell Mol. Biol. 8: 446-453

Barnes, P.J. 1986. Asthma as an axon reflex. Lancet. 40: 242-244.

Basbaum C. B. 1986. Regulation of airway secretory cells. Clinic. Chest Med. 7:231-237.

Brokaw J. J., Hillenbrand C. M., White G. W., McDonald D. M. 1990 Mechanism of tachyphylaxis associated with neurogenic plasma extravasation in the rat trachea. Am. Rev. Respir. Dis. 141:1434-40

Erjavec F., Lembeck F., Florjanc-Irman T. 1981. Release of histamine by substance P. Naunyn Schmiedebergs Arch. Pharmacol. 317: 67-70

Gamse R., Holzer P., Lembeck F. 1980. Drecrease of substance P in primary afferent neurons and impairment of neurogenic plasma extravasation by capsaicin. Br. J. Pharmacol. 68: 207-213

Guo J. J., Wang D. S., Huang H. T. 2003. Spontaneous remission of edema and regranulation of goblet cells in rat trachea after capsaicin-induced acute inflammation. Anat. Embryol. 206:301-309

Holzer P. 1988. Local effector functions of capsaicin-sensitive sensory nerve endings: involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides. Neuroscience 24:739-68

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

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


Huang H.T., Huang S. H., Luor Y. G. 1995. Postvagotomy changes in neurogenic plasma extravasation in rat bronchi. J. Auton. Nerv. Syst. 55: 9–17

Jancso, G., Kiraly E., Jancso-Gabor A. 1977. Pharmacologically induced selective degeneration of chemosensitive primary sensory neurons. Nature (Lond) 270: 741-743

Jeffery P. and Reid L. 1975. New observations of rat airway epithelium: A quantitative and electron microscopic study. J. Anat. 120: 295-320

Kiernan J. A. 1977. A study of chemically induced inflammation in the skin of the rat. Q. J. Exp. Physio. 62: 151-161

Kuby J. 1992. Immunology. pp.366-367. Freeman co. press, U.S.A.

Kuo H. ., Rohde J. A. L., Tokuyama K., Barnes P. J. and Rogers D. F. 1990. Capsaicin and sensory neroeptide stimulation goblet cell secretion in guinea pig tachea. J. Physiol. ( lond ) 431, 629-641.

Lembeck F. and Holzer P. 1979. Substance P as a neurogenic mediator of antidromic vasodilation and neurogenic plasma extravasation. Naunyn-Schmiedebergs Arch. Pharmacol. 310: 175-83

Lundberg J.M., Saria A. 1983., Capsaicin-induced desensitization of airway mucosa to cigarette smoke, mechanical and chemical irritants. Nature (Lond) 302: 251–253

McDonald D. M. 1987. Neurogenic inflammation in the respiratory tract: actions of sensory nerve mediators on blood vessels and epithelium of the airway mucosa. Am. Rew. Respir. Dis. 136:S65-S72.

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

McDonald D. M. 1988b. Respiratory tract infections increase susceptibility to neurogenic inflammation in the rat trachea. Am. Rev. Respir. Dis. 137: 1432–1440.

Moreno, J. E., and P. W. Mantyh. 1986. Mechanics of airway narrowing. Am. Rev. Respir. Dis. 133: 1171-1180.
Nadel J. A. 1992. Regulation of neurogenic inflammation by neutral endopeptidase. Am. Rev. Respir. Dis. 145:S48-S52

Nemmar A., Delaunois A., Beckers J.F., Sulon J., Bloden S., Gustin P. 1999. Modulatory effect of imetit, a histamine H3 receptor agonist, on C-fibers, cholinergic fibers and mast cells in rabbit lungs in vitro. Eur. J. Pharmacol. 371:23-30

Newman TM, Robichaud A, Rogers DF. 1996. Microanatomy of secretory granule release from guinea pig tracheal goblet cells. Am. J. Respir. Cell. Mol. Biol. 15(4):529-39.

Nicholls J. G., Martin A. R., Wallace B. G. 1992., From neuron to brain. 3rd ed. p.p. 272-274. Sinauer press, U.S.A.

Persson C. G. A. 1986., Role of plasma exudation in asmatic airways. Lancet 42: 1126-1128.

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

Saria A., Lundberg J.M. 1983. Evans blue fluorescence: quantitative and morphological evaluation of vascular permeability in animal tissues. J. Neurosci. Methods. 8: 41–49

Sertl K., Wiedermann C. J., Kowalski M. L. 1988. Substance P: the relationship between receptor distribytion in rat lung and the capacity of substance P to stimulate vascular permeability. Am. Rev. Respir. Dis. 138:151-159

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

Takeyama K., Tamaoki J., Nakata J., and Konno K. 1996. Effect of oxitropium bromide on histamine-induced airway goblet cell secretion. Am. J. Respir. Crit. Care. Med.154:231-6