纖維連結蛋白在廣東住血線蟲誘發的嗜伊紅性腦膜炎伴隨血-腦脊髓液障壁損壞之變化

Changes of fibronectin in Angiostrongylus cantonensis-induced eosinophilic meningitis accompany with blood-CSF barrier disruption

周峻暉(Chun-Hui Chou)

指導教授 ： 賴世展

中山醫學大學/醫學院/醫學研究所/碩士(2013年)

https://doi.org/10.6834/CSMU.2013.00008

摘要

腦脊髓液（cerebrospinal fluid, CSF）中的纖維連結蛋白（fibronectin）在正常的生理情況下呈現相當低的濃度，而在腦膜炎則會明顯增加。本研究結果顯示在廣東住血線蟲(Angiostrongylus cantonensis)感染鼷鼠引起的腦膜炎，纖維連結蛋白改變量最大的時間正好是血-腦脊髓液障壁（blood-CSF barrier）損傷最嚴重的時間點。同時，被降解的纖維連結蛋白濃度與滲入蜘蛛膜下腔的嗜伊紅性白血球(eosinophil)數量有關。組織免疫的結果顯示基質金屬蛋白酶-9（matrix metalloproteinase-9, MMP-9）分佈在脈絡叢的上皮細胞。免疫共同沉澱結果亦證實纖維連結蛋白與MMP-9有交互作用。進一步以MMP-9螯合劑GM6001處理被廣東住血線蟲感染的鼷鼠，結果顯示纖維連結蛋白降解的量、blood-CSF barrier通透性和嗜伊紅性白血球數量明顯減少。降解的纖維連結蛋白減少可能使經由blood-CSF barrier滲入蜘蛛膜下腔的嗜伊紅性白血球減少。這些結果顯示降解的纖維連結蛋白出現在致病的CSF中似乎與嗜伊紅性腦膜炎的嚴重程度有關，降解的纖維連結蛋白增加可能與腦障壁損傷有關，進而促使嗜伊紅性白血球滲入和移行至蜘蛛膜下腔。

關鍵字

廣東住血線蟲 ； 血-腦脊髓液障壁 ； 纖維連結蛋白 ； 腦膜炎

並列摘要

The concentrations of fibronectin which physiologically are present at relatively low levels in the cerebrospinal fluid (CSF) and often increased in meningitis. In this study, fibronectin degradation was coincided with the increased permeabilities of blood-CSF barrier. Also, the degradation of fibronectin was coincided with the formation of eosinophil infiltrates in angiostrongyliasis meningitis. Immunohistochemistry showed that MMP-9 localized in the epithelium of choroid plexus. Co-immunoprecipitation demonstrated that fibronectin avidly binds MMP-9. Furthermore, treatment with MMP-9 chelator GM6001 was significantly reduced fibronectin degradation, blood-CSF barrier permeability and eosinophil counts. The decrease of fibronectin degradation in CSF probably reflects decreased cellular invasion of the subarachnoid space across the blood-CSF barrier. These results suggested that the increased degradation of fibronectin might be associated with barrier disruption and also play a role in the extravasation and migration of eosinophils into the subarachnoid space during experimental parasitic infection.

並列關鍵字

Angiostrongylus cantonensis ； blood-CSF barrier ； fibronectin ； meningitis

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