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  • 學位論文

髓鞘蛋白在廣東住血線蟲感染鼷鼠造成發炎性脫髓鞘之變化

Alterations of myelin proteins in inflammatory demyelination of BALB/c mice caused by Angiostrongylus cantonensis

指導教授 : 賴世展

摘要


廣東住血線蟲(Angiostrongylus cantonensis)主要侵犯非適當宿主的中樞神經系統(central nervous system, CNS)造成嗜伊紅性腦膜炎或腦膜腦炎,隨著疾病的進展導致嚴重慢性脫髓鞘症 (demyelinating disease)。本試驗為了證實感染廣東住血線蟲導致脫髓鞘作用,分析廣東住血線蟲感染與未感染鼷鼠腦部與類腦脊髓液(cerebrospinal fluid, CSF)-like fluid 內髓鞘特異性標幟酵素(2', 3'-cyclic nucleotide 3'-phosphodiesterase, CNP)和髓鞘蛋白包括髓鞘相關醣蛋白(myelin-associated glycoprotein, MAG),髓鞘鹼性蛋白(myelin basic protein, MBP),髓鞘相關寡樹突鹼性蛋白(myelin-associated oligodendrocytic basic protein, MOBP)與類脂質蛋白(proteolipid protein, PLP)表現量之變化。本試驗發現,廣東住血線蟲感染鼷鼠誘發之嚴重嗜伊紅性腦膜炎或腦膜腦炎,類腦脊髓液 CNP 表現量比未感染鼷鼠有顯著的增加,免疫組織化學標幟顯示 CNP 分佈在寡樹突神經膠質細胞的細胞質,結果顯示CNP 的表現與廣東住血線蟲感染誘發中樞神經系統之脫髓鞘有關。同時,在廣東住血線蟲感染鼷鼠腦部,發現 MAG、MBP、MOBP 與 PLP mRNAs 之表現量有顯著的減少,反而其相對應之髓鞘蛋白在類腦脊髓液內表現量卻有顯著的增加,而在腦膜腦炎期間以光學顯微鏡觀察鼷鼠大腦發現血管周圍有發炎細胞浸潤(perivascular inflammatory infiltrates),研究結果顯示廣東住血線蟲感染導致脫髓鞘,推測為免疫系統活化攻擊寡樹突神經膠質細胞形成的髓鞘,導致髓鞘被破壞隨後髓鞘蛋白釋放至腦脊髓液內。因此,廣東住血線蟲感染造成腦內髓鞘被破壞可能是炎症介質(inflammatory mediators)參與其反應導致類腦脊髓液內之髓鞘蛋白的增加。

並列摘要


Angiostrongylus cantonensis causes meningoencephalitis, eosinophilic meningitis and persistent central nervous system (CNS) stimulation, resulting in a chronic demyelinating disease in non-permissive hosts. To define the course of demyelination caused by A.cantonensis, we analyzed the expression of 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNP), and myelin proteins including myelin-associated glycoprotein (MAG), myelin basic protein (MBP), myelin-associated oligodendrocytic basic protein (MOBP), and proteolipid protein (PLP) in brain and cerebrospinal fluid (CSF)-like fluid of infected and uninfected BALB/c mice. CNP in mouse CSF-like fluid was significantly upregulated in the severe phase of meningoencephalitis or meningitis as compared with controls. Immunohistochemistry localization showed that CNP was distributed in the cytoplasm of oligodendrocytes. These results showed that CNP was associated with A.cantonensis-induced demyelination of CNS. Additionally, in A.cantonensis- infected mice, the expression of MAG, MBP, MOBP, and PLP mRNAs in brain tissue were decreased, while expression of the corresponding proteins were significantly increased in mice CSF-like fluid. Light microscopy revealed perivascular inflammatory infiltrates in the brain during meningoencephalitis, suggesting that the cause of demyelination in angiostrongyliasis was immune system attack on the oligodendrocytic myelin sheath and subsequent release of myelin proteins into the CSF. Thus, intracerebral myelin breakdown in angiostrongyliasis may be a response to inflammatory mediators and the cause of increased myelin proteins in the CSF-like fluid.

並列關鍵字

Angiostrongylus cantonensis Demyelination meningoencephalitis CNP MAG MBP MOBP PLP.

參考文獻


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