臺灣博碩士論文加值系統

本研究顯示廣東住血線蟲誘發嗜伊紅性白血球浸潤增殖及發炎反應是經由JAK(Janus kinase)/STAT1(signal transducer and activator transcription), IAP(Inhibitor of apoptosis)/NF-κB(nuclear factor kappa binding protein)與MEKK1(mitogen activation protein/ERK kinase kinase)/JNK(c-Jun N-terminal kinases)等訊息傳遞因子有關。實驗以60隻廣東住血線蟲第三期幼蟲(L3)經口胃管灌入感染小白鼠，結果顯示這些訊息因子JAK/STAT1, IAP/NF-κB 與MEKK1/JNK等活化效應於感染後第3天開始增加，在第12或15天達到最大量。分別為磷酸化JAK及JNK、STAT1、IAP、NF-κB和MEKK1等蛋白含量各是4.7-，13-，1.9-，11.3-，10.3-，2.0-倍有顯著增加。而於控制組與感染組小白鼠之Raf、MEK1、ERK1/2(extracellular signal-related kinases)及p38等MAPK(mitogen-activated protein kinase)之結果則顯示沒有顯著差異。另外利用gelatin-substrate zymography分析，基質金屬蛋白酶-9(Matrix metalloproteinases, MMP-9)活性於感染後第12天表現，於第15天達到高量，其活性表現強度與嗜伊紅性白血球增殖呈正相關。此結果於感染小白鼠腦部組織病理學上發現嗜伊紅性白血球及嗜中性白血球浸潤，肉芽腫反應之時間點是一致的。基於以上之結果我們推測感染廣東住血線蟲引起嗜伊紅性白血球增多，可能是經由細胞激素活化JAK/STAT1，或氧化壓力活化MEKK1/JNK，或是促進IAP蛋白表現活化NF-κB所造成腦部組織的傷害。

Eosinophilic meningitis or meningoencephalitis caused by Angiostrongylus cantonensis is endemic to the Pacific area of Asia, especially Taiwan, Thailand, and Japan. Although eosinophilia is an important clinical manifestation of A. cantonensis infection, the role of eosinophils in the progress of the infection remains to be elucidated. In this experiment, we show that A. cantonensis-induced eosinophilia and inflammation might lead to the induction of IAP/NF-κB, JAK/STAT1 and MEKK1/JNK signals. The phosphorylation levels of JAK and JNK, STAT1, IAP, NF-κB and MEKK1 protein products were significantly increased by 4.7-, 13-, 1.9-, 11.3-, 10.3- and 2.0- fold, respectively, after 12 days or 15 days of A. cantonensis infection. However, no significant differences in MAPKs such as Raf, MEK-1, ERK1/2 and p38 expression were found between control and infected mice. The activation potency of JAK/STAT1, IAP/NF-κB and MEKK1/JNK started increasing on day 3, significant induction on days 12 or day 15 after A. cantonensis infection. Consistent results were noted in the pathological observations, including eosinophilia, leukocyte infiltration, granulomatous reactions, and time responses in the brain tissues of infected mice. These data suggest that the development of brain injury by eosinophilia of A. cantonensis infection is associated with activation of JAK/STAT1 signals by cytokines, and/or activation of MEKK1/JNK by oxidant stress, and/or activation of NF-κB by increasing IAP expression.

part-1
摘 要…………………………………………………………………… 2
Abstract………………………………………………………………… 4
目 錄…………………………………………………………………… 6
研 究 動 機…………………………………………………………… 7
前 言…………………………………………………………………… 9
材 料 與 方 法 ………………………………………………………22
結 果……………………………………………………………………28
討 論……………………………………………………………………31
結 論……………………………………………………………………36
圖 表 及 說 明 ………………………………………………………37
參 考 文 獻……………………………………………………………50
part-2
摘 要……………………………………………………………………68
Abstract…………………………………………………………………69
目 錄……………………………………………………………………70
研 究 動 機……………………………………………………………71
前 言……………………………………………………………………72
材 料 與 方 法 ………………………………………………………74
結 果……………………………………………………………………80
討 論……………………………………………………………………82
結 論……………………………………………………………………85
圖 表 及 說 明 ………………………………………………………86
參 考 文 獻……………………………………………………………92

part-1
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part-2
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