【摘要】

神經源性發炎症,簡稱為神經性發炎為經由感覺神經的軸突反射（axon reflex）而引發的急性發炎反應，而所伴隨的血漿外洩反應稱之為神經性血漿外洩（neurogenic plasma extravasation）。而此反應可見於哺乳動物的眼睛，舌尖，呼吸道，食道，膀胱，關節等部位。而過去研究神經性發炎方法，乃利用電刺激神經，吸入有刺激性的物質，或藉由靜脈注射刺激性物質，就之前研究呼吸道神經性發炎反應而言，其黏膜的感覺神經末梢會釋放出神經傳遞物質，例如：物質P會使得小靜脈的內皮細胞之間隙擴大形成內皮隙，造成血管通透性增加，使大量血漿外洩逸至血管外的結締組織之中造成組織水腫，也造成呼吸道平滑肌收縮，黏液分泌增加等改變。
利用血漿外洩的特性，來研究鼠類的呼吸道神經性發炎反應已相當普遍，但在食道的研究卻少有報告，現已知大鼠食道黏膜層與黏膜下層間有對物質P具免疫活性的感覺軸突。這些感覺神經軸突在神經性發炎反應扮演相當重要的角色，所釋放的物質P可經由擴散作用到小靜脈內皮細胞的接受器，引起細胞收縮形成內皮隙，而造成血漿外洩，而物質P的釋放經之前學者研究，可藉由辣椒素的刺激感覺神經元而釋出。
本篇報告是利用血漿外洩的特性，用辣椒素（90 μg/ml/kg）及物質P（3 μg/ml/kg）作為誘發食道發炎的刺激物，並以印地安染劑來標識血漿外洩的小靜脈。以整體封裝（whole mount）處理後，算出其面積密度，作為評估血漿外洩程度，並且也將組織做切片處理，觀察組織的病理變化。
實驗結果顯示：辣椒素及物質P確實造成了食道的神經性發炎，並造成血漿外洩，印地安染劑展現出許多滲漏小靜脈，在食道的滲漏小靜脈大多為長條形，分支甚多，彼此連接成網狀，分布在喉咽的滲漏小靜脈則呈細小而密集，在組織切片見到的是，黏膜下層結締組織有明顯的水腫現象。辣椒素(90 μg/ml/kg)及物質P (3 μg/ml/kg)造成的食道上段、中段及下段的急性發炎的程度，面積密度都超過20﹪，這情況都屬於強烈的發炎反應。食道各段血漿外洩程度沒有差異，但都造成結締組織明顯的水腫，而且都遠大於溶劑造成的血漿外洩。本實驗也同時證實辣椒素及物質P會同時造成食道及呼吸道的神經性發炎，可能與迷走神經的分支皆有支配於這兩處有關。

【Abstract】

Neurogenic inflammation is an acute inflammatory tissue response, that is mediated by sensory axon reflex. Accompanied with neurogenic inflammation, plasma extravasation, occurs in the eyes, esophagus, bladder, joints, the tip of tongue, and the respiratory tract of the mammal. Recently, many studies have investigated the neurogenic inflammation by electrical stimulation of nerves and intravascular injection of irritants. Upon stimulation, the sensory nerve endings in mucosa can release neuropeptides such as substance P, that causes formation of the venular endothelial gaps, plasma extravasation and tissue edema in various organs. Substance P also cause smooth muscle contraction and mucus secretion in the respiratory tract.
Neurogenic plasma extravasation has been studied extensively in the trachea, and bronchi, but rarely in the esophagus. It is known that a plexus of substance P-immunoreactive axons exists in the mucosal and submucosal layers. They play an important role in releasing substance P to act on the receptors of the venular endothelium through diffusion.
Based on plasma extravasation and other studies related to the respiratory tract, the purpose of the present study was to investigate neurogenic inflammatory response in the esophagus of the digestive tract. In this study, capsaicin (90 µg/ml/kg) and substance P (3 µg/ml/kg) were used as the irritant and inflammatory mediator, respectively to reduce neurogenic inflammation in the esophagus. India ink was used to label the affected venules. The magnitude of the neurogenic inflammation was expressed as area density of India ink-labeled leaky venules. Histopathological changes in the esophageal tissue were studied under the light microscope.
The result of this study indicated that capsaicin at the dose of (90 µg/ml/kg) and substance P at the dose of (3 µg/ml/kg) caused similar magnitude of inflammation in the esophagus. India ink-labeled venules distributed like a network in the mucosal tissue and in connective tissue of the submucosal layer. The upper, middle and lower parts of esophagus exhibited the same degree of inflammatory response, that was similar to that in the lower respiratory tract as the previous studies reported. These results suggest that nerve branches from the vagal trunk send sensory axons to innervate both the esophagus and airways.

【目錄】

中文摘要------------------------------------------1
英文摘要------------------------------------------3
緒言----------------------------------------------4
本論文的研究策略----------------------------------12
研究目的------------------------------------------14
材料與方法----------------------------------------15
結果----------------------------------------------20
討論----------------------------------------------24
結論----------------------------------------------28
參考文獻------------------------------------------29
圖------------------------------------------------35
表------------------------------------------------52

【參考文獻】


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