蔡崇弘賴世展林毅傑Yi-Chieh醫學研究所2026-10-289999-12-312011https://handle.ncl.edu.tw/11296/9zyhnmhttps://scholars.csmu.edu.tw/handle/123456789/35641脈絡叢上皮細胞（choroid plexus epithelial cells）間的緊密連結蛋白（tight junctions）是構成血液-腦脊髓液障壁（blood-cerebrospinal fluid barrier, BCB）的主要結構。蛋白酶體（proteasome）主要作用是降解細胞中不需要的或受到損傷的蛋白質。當廣東住血線蟲（Angiostrongylus cantonensis）感染非適宜宿主，會引起腦膜腦炎及BCB 的瓦解。本研究以廣東住血線蟲感染鼷鼠為模型，觀察到蛋白酶體的表現量在感染期間明顯增加。以免疫螢光染色法發現緊密連結蛋白閉合蛋白（occludin）和基質金屬蛋白酶-9（matrix　metalloproteinase-9, MMP-9） 在脈絡叢有相同的分布，並以共同免疫沉澱法證明閉合蛋白和MMP-9 有交互作用。並分別給予蛋白酶體活性抑制劑MG132 1.5 及3.0mg/kg/day，觀察到磷酸化的IκBα 及NF-κB減少。除此之外，MMP-9 的活性及閉合蛋白的降解也因為MG132 的作用而減少。綜合上述，當鼷鼠受到廣東住血線蟲感染而引發嗜伊紅性腦膜腦炎時，蛋白酶體是透過降解磷酸化的IκBα 來調節NF-κB 的活化，進而來調控下游MMP-9 的作用及閉合蛋白的降解。The tight junctions in the epithelial cell of the choroids are the major structures of the blood-cerebrospinal fluid barrier (BCB). The major function of proteasome is to degrade unneeded or damage proteins by proteolysis. Disruption of BCB and resulted in meningoencephalitis areimportant pathological events in non-permissive hosts caused by Angiostrongylus cantonensis. In this study, five-week BALB/c mice were infected with the third-stage larvae of A. cantonensis. The results showed the protein levels of proteasome were increased during A. cantonensis infection. Occludin was co-locolized with matrix metalloproteinase-9(MMP-9) by confocal immunoflourescence microscopy. Further, we demonstrated that occludin interacted with MMP-9 in brain tissue of infected-mice by co-immunoprecipitation. Theinfected-mice were treated with proteasomal activity inhibitor MG132 in 1.5 and 3.0 mg/kg/day, respectively. The protein levels of phosphorylated IκBα were significantly decreased (P<0.05) as compared with untreated control. Also, phosphorylated nuclear factor kappa-light-chain-nhancer of activated B cells (NF-κB) has similar result. In addition, activity of MMP-9 and occludin degradation were reduced because of MG132. The role of proteasome in A. cantonensis infection is to degrade phosphorylated IκBα, and modulate phosphorylated NF-κB, and then regulate the activation of MMP-9 and occludin degradation.thesis