內毒素為一種脂多醣（lipopolysaccharide，簡稱為LPS），來自革蘭氏陰性菌細胞壁的毒性化學物質，可活化NF-κB，並刺激免疫細胞釋放細胞介素（cytokine）。這些前發炎媒介物進而引起全身性急性發炎反應、個體多重器官衰竭與敗血性休克症狀。內毒素可以增加微血管通透性並誘發小靜脈內皮層形成內皮隙，並造成血漿外洩，蓄積在結締組織而形成水腫。而在發炎反應的過程中，血管系統的血漿滲漏是一個重要的指標。哺乳類的消化系統的上皮組織存在大量的杯狀細胞，其分泌的黏液除了浸潤食糜之外，亦可形成一道屏障，保護消化道的上皮組織免於受到物理及化學性的傷害。杯狀細胞排放黏液反應受到許多的因素所調節，包含了：刺激性氣體、神經活化、氧化自由基與發炎媒介因子。

本實驗的重點在於：(1) 研究靜脈注射高劑量LPS (15 mg/kg ) 對
於小腸血漿滲漏程度及杯狀細胞分泌作用的影響。(2) α2-腎上腺素受器之拮抗劑 urethan 是否對於 LPS 所引起的血漿滲漏及黏液分泌發揮抑制作用。本實驗利用靜脈注射發炎追蹤劑印地安墨汁來標定血漿滲漏的血管，將小腸組織以 3μm 厚度的切片及 Alcian blue-PAS 染色法來呈現黏液中的醣蛋白，用以觀察杯狀細胞的分泌作用。實驗結果顯示，靜脈注射 LPS 不僅引起小腸組織的血漿滲漏並且伴隨著高比率的杯狀細胞分泌作用，相較於注射生理食鹽水之對照組皆高出約三倍的量，而分泌之黏液會大量的堆積在絨毛間隙中。以 α2-腎上腺素受器之拮抗劑 urethan 前處理，可明顯的抑制 LPS 所引起的血漿滲漏與黏液分泌之現象，相較於單獨施予靜脈注射 LPS 之組別，可抑制血漿滲漏達 45-50%，黏液分泌達 25-30% 之程度。由實驗結果推論，靜脈注射高劑量的內毒素所引起的敗血性休克中，小腸會發生血漿滲漏及杯狀細胞的過度分泌的反應，並且伴隨著 α2-腎上腺素受器的活化。

Lipopolysaccharide (LPS) is the toxic chemical component of the cell wall in all gram-negative bacteria which can activate NF-κB, also stimulate immune cells to release cytokines. These pro-inflammatory mediators induce systemic acute inflammation, multiple organs dysfunction syndrome（MODS）and sepsis. LPS could increase the permeability of capillary, and cause the acute formation of numerous endothelial gaps among venular endothelial cells that result in extensive plasma leakage in the inflammatory tissues. Plasma leakage from microvasculature is a hallmark of inflammation. Mammalian intestines have many goblet cells that synthesize mucus and discharge it into the intestinal lumen. The mucus film that covers the surface epithelium facing the lumen of digestive system, is an immune defense that can prevent gastrointestinal epithelium from chemical and physical damage and act as a lubricant. Goblet cells can discharge mucins in response to a wide variety of stimuli, including irritant gases, nerve activation, reactive oxygen species, inflammatory mediators.
This study was aimed to investigate : (1) The degree of plasma leakage and goblet cell secretion in the small intestine of rats after an intravenous injection of a high dose of LPS (15 mg/kg), (2) The effect of α2-adrenergic receptors antagonist, urethan, on endotoxin-induced plasma leakage and goblet cell secretion. For the study of plasma extravasation in small intestine during endotoxemia, India ink was used as the tracer to mark the inflamed leaky microvessels. The sections of the small intestine 3μm in thickness were stained with Alcian blue and periodic acid-Schiff reagent to detect glycoproteins of goblet cells. Our results showed that LPS not only caused an increase in plasma leakage but also triggered degranulation of many goblet cells in the small intestine. LPS augment the expression of plasma leakage and mucus secretion for three times. A large amount of extracellular mucus was accumulated between intestinal villi after LPS stimulation. Pretreatment with urethan, the α2-adrenergic receptor antagonist, significantly inhibited plasma leakage by 40-50% and goblet cell secretion by 25-30% induced by endotoxin. It is concluded that the plasma leakage and goblet cell hypersecretion induced by endotoxin shock was outstanding and associated with activation of α2-adrenergic receptors.

【中文摘要】…………………………………………………..i
【Abstract】……………………………………………………iii
【目錄】………………………………………………………...v
【諸論】……………………………………………………….1
【研究目的】…………………………………………………17
【材料與方法】………………………………………………18
【實驗結果】…………………………………………………24
【討論】………………………………………………………30
【參考文獻】…………………………………………………38
【圖表】………………………………………………………51

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