基質金屬蛋白酶-12在BALB/c鼷鼠感染廣東住血線蟲誘發嗜伊紅性腦膜炎或腦膜腦炎之致病機轉

廣東住血線蟲(Angiostrongylus cantonensis)，又稱之為鼠肺線蟲，感染宿主後常誘發嗜伊紅性腦膜炎或腦膜腦炎。在過去的研究指出，基質金屬蛋白酶-9(matrix metalloproteinase-9)參與嗜伊紅性腦膜炎或腦膜腦炎疾病的發展過程。本篇試驗中，我們利用五週大的BALB/c品系的雄鼠感染廣東住血線蟲，結果顯示在感染組鼷鼠的腦部組織及腦脊隨液中，皆發現基質金屬蛋白酶-12蛋白表現量從感染後第五天起有明顯的增加。同樣的，基質金屬蛋白酶-12的受質elastin其表現量也有增加的趨勢。藉由組織免疫染色實驗確認基質金屬蛋白酶-12分佈在浸潤至蜘蛛膜下腔的白血球中，主要在巨噬細胞及嗜伊紅性白血球。治療組的鼷鼠於感染後的第五及第十五天分別給予每天每公斤10毫克的驅蟲藥albendazole、每天每公斤30毫克的基質金屬蛋白酶抑制劑doxycycline或是albendazole與doxycycline的混合治療，連續給藥七天。治療效果方面，發現在感染後五天混合治療組白血球浸潤現象明顯減少，基質金屬蛋白酶-12的表現量相較於感染組也有明顯的降低。試驗結果指出基質金屬蛋白酶-12可能也參與由廣東住血線蟲誘發的嗜伊紅性腦膜炎或腦膜腦炎疾病發展過程。此外，新的藥物組合對於廣東住血線蟲誘發的嗜伊紅性腦膜炎或腦膜腦炎提供另一種治療用藥的選擇。

Angiostrongylus cantonensis, the rat lugworm, is the principal cause of eosinophilic meningitis or meningoencephalitis. In the previous study, matrix metalloproteinase-9 (MMP-9) has been proved involved in the pathogenesis of eosinophilic meningitis or meningoencephalitis. In this study, we used 5-week BALB/c male mice infected 50 A. cantonensis larvae. The results showed that MMP-12 is found in the brain tissues and cerebral spinal fruid (CSF) of infected mice and significantly increases from day 5 PI. Similarly, the expression of elastin, the substrate of MMP-12 is also increased. By immunohistochemistry, confirmed that MMP-12 distributed in leukocytes that infiltrated into subarachnoid space and mainly expressed in macrophages and eosinophils. The mice treated with albendazole (10mg/kg per day) alone, doxycycline (30mg/kg per day) alone, or a combination of albendazole (10mg/kg per day) and doxycycline (30mg/kg per day) for 7 consecutive days on day 5 and 15 post-inoculation (PI), respectively. The treatment of albendazole-doxycycline co-therapy on day 5 PI significantly reduced the infiltration of leukocytes and the expression of MMP-12 in infected mice. These results suggested that MMP-12 may contribute to the develop of eosinophilic meningitis or meningoencephalitis caused by A. cantonensis. This new approach may be beneficial to treat the parasitic meningitis or meningoencephalitis.