【摘要】
神經性發炎反應可藉由感覺神經被活化所釋放之神經傳導物質而誘發，如：tachykinins和CGRP。神經受辣椒素的刺激可誘發感覺神經產生一個重要的神經傳導物質—物質P，其可與血管內皮細胞上的NK1受器結合造成血管血漿外洩的現象。熱休克蛋白為一個多保留基因的分子，在細胞遭受到壓力時扮演保護的角色。藉由全身性熱休克可誘發氣管、食道增加熱休克蛋白的產量，並且可維持其活性達6天。在過去的研究指出，全身性熱休克處理可以減輕大鼠受過敏反應引發的血漿蛋白外洩及減弱低血壓的癥狀。

為了了解熱休克處理與神經性發炎之間的關係，本實驗對大鼠進行全身性熱休克前處理，當大鼠體溫達42 ℃左右維持溫度15分鐘；隔天，以辣椒素（90μg/ml/kg）或物質P（3μg/ml/kg）靜脈注射引發神經性發炎反應。以India ink標識血漿外洩的血管計算其面積密度，比較血漿外洩程度。結果明顯表示：經熱前處理隔一天之大鼠對於辣椒素引起之發炎反應比對照組減少了50 ~ 67%；對於物質P引起之發炎反應亦減少約33 %。但經熱前處理後隔六天之大鼠對於神經性發炎反應並無抑制作用。以西方墨點法分析經熱處理大鼠之氣管及食道熱休克蛋白HSP70量，發現其在經全身性熱休克處理隔一天時大量表現，相反地，在熱處理隔六天時則表現量減少。因此實驗結果推測全身性熱休克處理會造成組織增產熱休克蛋白，來影響物質P對於血管內皮細胞上NK1受器的親和力而抑制了血漿外洩。

【Abstract】
Neurogenic inflammation can be initiated by activation of sensory nerves to release neuropeptides, including tachykinins and calcitonin gene-related peptide. Capsaicin stimulation induces the release of substance P, the most important tachykinin and other neurotransmitters from sensory nerves to cause an increase of plasma leakage via the binding of substance P to NK1 receptors on endothelial cells. It has been proven that hyperthermic pretreatment decreases microvascular protein leakage and attenuates hypotension in anaphylactic shock in rats. Heat shock proteins（HSPs）are families of phylogenetically conserved molecules that have a protective role in all living cells under stress . Heat shock proteins are induced by whole-body hyperthermia and persist for 6 days.
To establish the relationship between heat shock and neurogenic inflammation, the present study investigated whether whole-body hyperthermia pretreatment, at 42 ℃ for 15 min in rats 1 day earlier, could suppress inflammatory response in the lower airways and esophagus evoked by capsaicin (90 µg/ml/kg) or substance P (3 µg/ml/kg ). The magnitude of neurogenic inflammation in the trachea and bronchi was expressed by the area density of India ink-labeled leaky blood vessels in the airway mucosa. One day after heat shock pretreatment, capsaicin-evoked inflammation was reduced by one half to two thirds, and reduced substance P-evoked inflammation by one third. Six days after exposure to heat shock, neurogenic inflammation was not inhibited. HSPs appeared overexpressed in trachea and esophagus tissue in the rats one day after hyperthermia, but was less expressed 6 days after hyperthermia.
It is suggested that exposure of the rats to whole-body hyperthermia caused an increased production of HSPs that might influence the affinity of the binding of substance P to NK1 receptors on venule endothelial cells, and reduce the amount of neurogenic plasma leakage.

目錄(index)
【前言】 1
一、神經性血漿外洩之機制 1
二、熱休克蛋白（Heat shock proteins, HSPs） 4
【研究目的】 7
【實驗流程】 8
一、實驗動物 8
二、全身性熱休克處理動物（whole-body hyperthermia pretreat） 8
三、誘發呼吸道神經性發炎反應（Induction of airway neurogenic inflammation） 9
四、熱休克蛋白之生化學測定 11
五、組織學研究 13
六、統計方法 14
【實驗結果】 15
一、注射辣椒素誘發上呼吸道及食道血漿外洩之情形 15
二、注射物質P誘發上呼吸道及食道血漿之外洩 16
三、熱休克蛋白之西方墨點法分析 18
四、氣管及食道組織切片之觀察 18
【討論】 20
一、全身性熱休克對於以辣椒素或物質P誘發呼吸道及食道神經性發炎之影響及機轉 20
二、全身性熱休克對於以辣椒素或物質P誘發全身性血壓下降之探討 22
三、熱休克蛋白和發炎反應之關係 22
【參考文獻】 24
【圖】 29

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