小鼠感染廣東住血線蟲後，腦脊髓液前列腺素E2濃度的變化

Kinetics of change in the prostaglandin E2 concentration in cerebrospinal fluid of mice infected with Angiostrongylus cantonensis

唐銘蔓(Ming-Man Tang)

指導教授 ： 顏全敏

高雄醫學大學/醫學院/醫學研究所/碩士(2006年)

摘要

廣東住血線蟲第三及第五期幼蟲，在含花生四烯酸的體外培養培養液中都含有高濃度的前列腺素E2，這表示蟲體具有COX酵素，能轉化花生四烯酸成為前列腺素E2，而該酵素活性不受阿斯匹靈等抑制劑的影響。另一方面，Balb/c鼷鼠感染的蟲體數越多，週邊血液及腦脊髓液內的嗜伊紅性白血球的數目會增加，腦脊髓液中的前列腺素E2濃度也顯著成正相關增加；而鼷鼠感染的天數越多，週邊血液及腦脊髓液內的嗜伊紅性白血球的數目及腦脊髓液中的前列腺素E2濃度也持續上升。但在感染前後持續口服阿斯匹靈，其週邊血液及腦脊髓液內的嗜伊紅性白血球的數目卻沒有顯著減少的現象，也無法有效降低腦脊髓液中前列腺素E2的生成，減輕其發炎的症狀，而且腦脊髓液及周邊血液的嗜伊紅性白血球也沒有明顯減少的情形，因此，我們可以推測廣東住血線蟲的COX酵素可能不屬於一般所熟知的COX-1和COX-2。所以，探討廣東住血線蟲的COX酵素及其抑制劑以降低前列腺素E2的合成，或許可以當作未來研究的方向。

關鍵字

廣東住血線蟲 ； 腦脊髓液 ； 前列腺素 ； 環氧酵素 ； 嗜伊紅性腦膜炎

並列摘要

Angiostrongylus cantonensis (the rat lung worm) is the principle cause of eosinophilic meningitis or meningoencephalitis worldwide. However, there is still something unknown about the molecules secreted by the parasite that modulate host immune responses or epithelial barrier function in the brain. The current investigation was undertaken to investigate whether any immunomodulatory compounds could be identified from secretions of A.cantonensis. It is considered that prostaglandin E2 (PGE2) is one of the compounds the parasite induced and cyclooxygenase (COX) enzymes are responsible for the biosynthesis of PGE2 depended on the metabolism of arachidonic acid (AA). Rescently, two COX isoforms have been cloned (COX-1 and COX-2) .Various studies suggest that aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) can inhibit the activity of cyclooxygenase enzymes. In vitro, live A.cantonensis was incubated with arachidonic acid and aid drugs like aspirin, indomethacin , nimesulide and SC560. Here it is found that A.cantonensis is involved in PGE2 production, but the inhibitors did not inhibit its COX activity.In vivo, mice was infected with A.cantonensis and then collected CSF of mice at different days. In this study, the concentration of PGE2 in the condition medium and CSF was determined by FPIA. It is found that the concentration of PGE2 is dose-dependent and time-dependent after infected with A.cantonensis. And COX-inhibitor like aspirin and indomethacin can’t inhibit the COX activity effectively and reduce the PGE2 production. It is considered that finding the COX-like inhibitor to reduce PGE2 concentration may be the way for relieving symptoms of eosinophilic meningitis in the future.

並列關鍵字

Angiostrongylus cantonensis ； cerebrospinal fluid ； prostaglandin ； cyclooxygenase ； eosinophilic meningitis

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