臺灣博碩士論文加值系統

論文摘要
氣喘不只影響呼吸道，同時也會影響中樞神經系統，以目前的醫療而言類固醇是治療氣喘相當重要的藥物。
在我們的研究，我們探討卵白蛋白(ovalbumin) 對腦部的急性影響，也探討甲基去氫氧化可體松(methylprednisolone)對過敏性氣喘老鼠肺部與中樞神經系統的影響。大鼠被卵白蛋白敏感化並且暴露於卵白蛋白氣霧下導致氣喘產生，我們比較在卵白蛋白氣霧曝露前腹膜注射甲基去氫氧化可體松與不注射甲基去氫氧化可體松的差異。結果，在卵白蛋白刺激下，c-Fos的量上升，glial fibrillary acidic protein (GFAP)也上升，但是neuronal nitric oxide synthase(nNOS)在孤立徑核( nucleus tractus solitarius )卻是下降的。此外，c-Fos，GFAP 和nNOS在海馬迴(hippocampus)是上升的，nNOS在嗅神經球(olfactory bulb)是上升的。然而在卵白蛋白刺激下，這些蛋白質在額葉和小腦皮質是沒有變化的;相反地，在卵白蛋白氣霧暴露前注射甲基去氫氧化可體松，這些蛋白質如c-Fos在海馬迴的cornu-ammonis 1 (CA1)地區、GFAP在孤立徑核、 nNOS在CA1與嗅神經球的表現是下降的，而nNOS在孤立徑核是上升的，這些發現表示過敏性氣喘大鼠在卵白蛋白的刺激下，腦部有反應，而且注射甲基去氫氧化可體松不僅改善呼吸道的發炎問題，同時也改善卵白蛋白造成的影響。
關鍵字：氣喘、腦部、甲基去氫氧化可體松、卵白蛋白

Abstract

Asthma affects not only the airways but also the central nervous system (CNS). Corticosteroids are effective therapeutic agents for asthma. In our study, we investigated the acute effect of ovalbumin (OVA) on the brain and the effectiveness of methylprednisolone (MP) in both the periphery and CNS in a rat model of allergic asthma. Rats sensitized to OVA and exposed to OVA aerosol challenge to induce allergic asthma were compared with control rats and rats sensitized to OVA and pretreated with MP before OVA exposure. In response to OVA stimulation, the amount of c-Fos and glial fibrillary acidic protein (GFAP) increased, while that of neuronal nitric oxide synthase (nNOS) decreased in the nucleus tractus solitarius (NTS). In addition, the c-Fos, GFAP, and nNOS levels in the hippocampus and the nNOS levels in the olfactory bulb increased. However,the expression of these proteins in the frontal and cerebellar cortices was not affected by OVA stimulation. In contrast,pretreatment with MP before OVA exposure decreased the protein expression of c-Fos in the CA1 area, GFAP in NTS, and nNOS in CA1 and olfactory bulb, and while it increased the nNOS content in the NTS. These findings suggest that the brain responds to OVA stimulation in a rat model of allergic asthma and that MP treatment can not only ameliorate airway inflammation but also OVA-induced effects.
Keywords: asthma; brain; methylprednisolone; ovalbumin

目　錄
Abstract 1
論文摘要 2
第壹章　序論 3
第一節　研究背景與動機 3
第二節　假設 3
第貳章　實驗方法與材料 4
第一節　實驗動物 4
第二節　氣喘大鼠動物模式之建立 5
第三節　實驗設計 6
第四節　組織取樣與蛋白質測定 7
第五節　統計分析 16
第參章　結果 17
第一節　甲基去氫氧化可體松可以改善大鼠呼吸道 17
第二節　甲基去氫氧化可體松可以抑制腦部c-Fos蛋白質的表現 19
第三節　甲基去氫氧化可體松可以抑制孤立徑核蛋白質的表現 22
第四節　甲基去氫氧化可體松可以改善腦部nNOS蛋白質的表現 25
第肆章　討論 28
第伍章　參考文獻 30
第陸章　致謝 32
附錄　本研究發表於Neuroscience Letters 440(2008)87-91的文章 32

[1] P.J. Barnes: Corticosteroids: mode of action and place in management, Asthma,4th edition. Edited by T.J.H. Clark,　S. Godfrey, T.H. Lee, N.C.　Thomson. London, A Hodder Arnold Publication, 2000, p304–328.
[2] A.S. Basso, F.A. Costa-Pinto, M. Russo, L.R. Britto, L.C. de S��-Rocha, J.
Palermo-Neto, Neural correlates of IgE-mediated food allergy, J. euroimmunol.
140 (2003) 69–77.
[3] A.C. Bonham, C.Y. Chen, T. Mutoh, J.P. Joad, Lung C-fiber CNS reflex: role in the respiratory consequences of extended environmental tobacco smoke exposure　in young guinea pigs, Environ. Health Perspect.109 (2001) 573–578.
[4] G.C. Brown, A. Bal-Price, Inflammatory neurodegeneration mediated by nitric oxide, glutamate, and mitochondria, Mol. Neurobiol. 27 (2003) 325–355.
[5] C.Y. Chen, A.C. Bonham, E.S. Schelegle, L.J. Gershwin, C.G. Plopper, J.P. Joad, Extended allergen exposure in asthmatic monkeys induces neuroplasticity in nucleus tractus solitarius, J. Allergy Clin. Immunol.108 (2001) 557–562.
[6] F.A. Costa-Pinto, A.S. Basso, L.C. de S��-Rocha, L.R. Britto, M. Russo, J.
Palermo-Neto, Neural correlates of IgE-mediated allergy, Ann. N. Y. Acad. Sci.
1088 (2006) 116–131.
[7] L.F. Eng, R.S. Ghirnikar, GFAP and astrogliosis, Brain Pathol. 4 (1994)229–237.
[8] L. Giovannelli, F. Casamenti, G. Pepeu, c-Fos expression in the rat nucleus basalis upon excitotoxic lesion with quisqualic acid: a study in adult and aged animals, J. Neural Transm.105 (1998) 935–948.
[9] R.D. Goodwin, D.M. Fergusson, L.J. Horwood, Asthma and depressive and anxiety disorders among young persons in the community, Psychol Med. 34
(2004) 1465–1474.
[10] D.A. Groneberg, D. Quarcoo, N. Frossard, A. Fischer, Neurogenic mechanisms
in bronchial inflammatory diseases, Allergy 59 (2004) 1139–1152.
[11] D. Jordan, Central nervous pathways and control of the airways, Respir. Physiol.125 (2001) 67–81.
[12] J.G. Martin, M. Suzuki, K. Maghni, R. Pantano, D. Ramos–Barbon, D. Ihaku, F.Nantel, D. Denis, Q. Hamid, W.S. Powell. The immunomodulatory actions of prostaglandin E2 on allergic airway responses in the rat. J. Immunol. 169 (2002)3693–3696.
[13] M.A. Rosenkranz, W.W. Busse, T. Johnstone, C.A. Swenson, G.M. Crisafi, M.M.Jackson, J.A. Bosch, J.F. Sheridan, R.J. Davidson, Neural circuitry underlying the interaction between emotion and asthma symptom exacerbation, Proc. Natl. Acad. Sci. U. S. A. 102 (2005) 13319–13324.
[14] L.W. Swanson, Brain Maps: Structure of the Rat Brain, Elsevier, New York.
1992.
[15] J. Thome, B. Pesold, M. Baader, M. Hu, J.C. Gewirtz, R.S. Duman, F.A. Henn, Stress differentially regulates synaptophysin and synaptotagmin expression in hippocampus, Biol. Psychiatry 50 (2001) 809–812.
[16] J.G. Wagner, J.A. Hotchkiss, J.R. Harkema, Enhancement of nasal inflammatory and epithelial responses after ozone and allergen coexposure in brown Norway rats, Toxicol. Sci. 67 (2002) 284–294.
[17] Y. Wu, H. Zhou, Y. Xu, S. Li. Enhanced expression of urocortin in lung tissues
of rats with allergic asthma, Biochem. Biophys. Res. Commun. 341 (2006)
532–540.