出版年:

研究生:

李一平

研究生(英文姓名):

Lee Yi-Ping

論文名稱:

鏈球菌致熱性外毒素A引起兔子之致熱作用及其作用位置

英文論文名稱:

Pyrogenicity of Streptococcal Pyrogenic Exotoxin A and Its Acting Site in Rabbits

指導教授:

翁舷誌

指導教授(英文姓名):

Won Shen-Jeu

學位類別:

碩士

校院名稱:

國立成功大學　

系所名稱:

微生物暨免疫學研究所

學號:

S46861042

學年度:

87

語文別:

中文

論文頁數:

69

關鍵詞:

鏈球菌致熱性外毒素A ; 發燒 ; 血管脈叢終端器官 ; 細胞素 ; 前列腺素E2 ; 兔子

英文關鍵詞:

Streptococcal pyrogenic exotoxin A ;
Fever ; Organum vasculosum laminae terminalis ;
Cytokine ; Prostaglandin E2 ; Rabbit

被引用次數:

1

[ 摘要 ]

化膿性鏈球菌 (Streptococcus pyrogenes) 是一種可以引起許多不同疾病的重要人類致病原。它們可以產生許多具有生物活性的毒素，包括：鏈球菌致熱性外毒素 (SPE) A、B、C、D、E、以及F。這些毒素因為可以對宿主的免疫系統產生廣泛的作用，所以被歸類為超級抗原 (superantigen)。SPE在鏈球菌性毒性休克症狀 (STSS) 的致病機轉上扮演了一個很重要的角色。在感染的初期，患者通常會產生高熱及多器官病害的病理徵狀，而導致患者的高死亡率。然而，SPEA的致熱作用及機轉至今仍然不清楚。本研究的目的是利用兔子的動物模式來探討由靜脈途徑或血管脈叢終端器官 (OVLT) 途徑施打SPEA後的致熱作用機轉。研究結果顯示：靜脈注射 (50-500 ng/kg) 或OVLT內注射 (0.2-5 ng/kg) 皆可引起兔子產生遲緩型、單峰、並有劑量相關性的發燒現象，而OVLT途徑僅需非常低的劑量即可引起和靜脈途徑相似的發燒。靜脈注射SPEA所引起的發燒現象可以被周邊事先給予cycloheximide (一種蛋白質合成酵素抑制劑)、dexamethasone (一種強效的抗發炎及免疫抑制劑)、indomethacin (一種環氧化酵素抑制劑)，及OVLT途徑事先給予cycloheximide、dexamethasone、indomethacin所抑制。OVLT內注射SPEA所引起的發燒現象可以被周邊事先給予cycloheximide，及OVLT途徑事先給予dexamethasone、indomethacin所抑制。在靜脈注射SPEA後，隨著兔子體溫的變化，血清中的腫瘤壞死因子 (TNF) 及介白質 (IL) -2有增加的現象。將兔子的周邊血單核細胞和SPEA一起培養，也可以在上清液中偵測到TNF、IL-1、及IL-2的增加。綜上實驗結果顯示SPEA引起兔子發燒的機制可能因SPEA誘發兔子產生TNF及IL-2或其他因子。而兔子腦部OVLT地區的cyclooxygenase (COX) pathway可能與SPEA引起兔子之致熱作用有密切的關係。

[ 英文摘要 ]

The gram-positive bacterium Streptococcus pyrogenes is the most important human pathogen causing a variety of diseases. It produces several biological active toxins including streptococcal pyrogenic exotoxin (SPE) A, B, C, D, E and F which have been shown to belong to the superantigens because of their erudite effects on the immune system. SPE are involved in the pathogenesis of streptococcal toxic-shock syndrome (STSS) with a high mortality including high fever and multiorgan failure in the early stage of infection. However, the mechanism and the mode of pyrogenicity of SPEA remains unclear. The purpose of this study is to assess the febrile responses of rabbits through intravenous or intra-organum vasculosum laminae terminals (intra-OVLT) administration of SPEA. Intravenous (50-500 ng/kg) or intra-OVLT (0.2-5 ng/kg) administration of SPEA produced a delayed-onset, monophasic and dose-related fever in rabbit. Compared with the febrile responses induced by intravenous injection of SPEA, the OVLT route of injection required a much lower dose of SPEA to produce a similar fever. The fever induced by intravenous injection of SPEA in rabbits was significantly attenuated by pretreatment with both of intravenous injection of cycloheximide (a protein synthetase inhibitor) or dexamethasone (an effective anti-inflammatory and immunosuppressive agent), or intraperitoneal injection of indomethacin (a cyclo-oxygenase synthetase inhibitor) and intra-OVLT injection of cycloheximide, dexamethasone or indomethacin. The fever induced by intra-OVLT injection of SPEA in rabbits was significantly attenuated by pretreatment with both of intravenous injection of cycloheximide and intra-OVLT injection of dexamethasone or indomethacin. In parallel with colonic temperature change, the circulating levels of tumor necrosis factor (TNF) and interleukin (IL) -2 in rabbits after SPEA injection were slightly increased. In addition, the levels of TNF, IL-1 and IL-2 in the supernatants from SPEA-treated rabbit peripheral blood mononuclear cells (PBMC) were also increased. The present results suggest that the fever induced by SPEA may mediate the increase in the circulating levels of TNF and IL-2 or other factors, and cyclooxygenase (COX) pathway in the OVLT may mediate the SPEA-induced febrile response in rabbits.