探討緊密黏著分子-A在鼷鼠感染廣東住血線蟲誘發腦膜腦炎之變化

Changes of junctional adhesion molecule-A in mice with meningoencephalitis caused by Angiostrongylus cantonensis

邱秉松(Ping-Sang Chiu)

指導教授 ： 蔡崇弘 ； 賴世展

中山醫學大學/醫學院/醫學研究所/碩士(2009年)

https://doi.org/10.6834/CSMU.2009.00018

摘要

血腦障壁（Blood-brain barrier）的功能是維持腦部正常功能，及控制血流中有害物質和細胞進入腦實質中。而緊密連結（tight junctions, TJs）是形成血腦障壁及調節完整度的要素之一。當非適當宿主感染廣東住血線蟲（Angiostrongylus cantonensis）時，引起的腦膜腦炎及血腦障壁的瓦解，是一個重要的病理現象。在本篇試驗中，以五週齡的雄性BALB/c鼷鼠，經口餵食感染廣東住血線蟲。結果顯示，以西方墨點法偵測腦實質及腦脊髓液（cerebrospinal fluid）中緊密連著分子-A（junctional adhesion molecule-A, JAM-A），在受到廣東住血線蟲感染時，其蛋白表現在感染的第15天、第20天及第25天與未感染組相比較有明顯上升的趨勢。以免疫共同沉澱法於腦實質觀察到，JAM-A的降解與基質金屬蛋白酶-9（matrix metalloproteinase-9, MMP-9）有關。進一步以免疫螢光染色發現，當受到廣東住血線蟲感染時，JAM-A的蛋白表現，會與MMP-9有交互作用。換句話說，也就是JAM-A蛋白的降解與MMP-9有關。這些結果顯示，當受到廣東住血線蟲感染引起的嗜伊紅性腦膜腦炎時，在緊密連結蛋白被瓦解，MMP-9扮演重要的角色。本試驗證明，當鼷鼠受到廣東住血線蟲感染誘發嗜伊紅性腦膜腦炎時，JAM-A可用來評估血腦障壁完整度的重要指標。

關鍵字

廣東住血線蟲 ； 緊密黏著分子-A ； 腦膜腦炎

並列摘要

Normal brain function is maintained and controlled by the blood-brain barrier (BBB), which is essential to limit the entry of potentially harmful molecules and cells from the blood into the brain parenchyma. Tight junctions are the main structural elements that regulate the BBB integrity. Disruption of BBB and induced meningoencephalitis in non-permissive hosts are important pathological events caused by Angiostrongylus cantonensis. In this study, 5-week BALB/c male mice infect with A. cantonensis. The results indicated that tight junction protein, junctional adhesion molecule-A (JAM-A) in the brain tissues of mice was significantly increased on days 15, 20 and 25 post-inoculation (PI) compared with uninfected mice. Similarly, the expression of JAM-A in cerebrospinal fluid (CSF) of mice was also increased at the same time points. Further, we demonstrated that JAM-A interacted with matrix metalloproteinase-9 (MMP-9) in brain tissue of infected mice by co-immunoprecipitation. Also, immunofluorescence staining of mice brain section revealed that JAM-A expression connected with MMP-9 on 20 PI. These results suggest that JAM-A degradation in mice with meningoencephalitis was mediated by MMP-9. This study demonstrated that JAM-A may be an important factor in meningoencephalitis of BALB/c mice caused by A. cantonensis and it can evaluate BBB integrity.

並列關鍵字

Angiostrongylus cantonensis ； junctional adhesion molecule-A ； meningoencephalitis

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