間質蛋白分解酵素-9被認為參與廣東住血線蟲感染造成的腦膜炎。雖然目前已有一些驅蟲藥可用於治療廣東住血線蟲感染的患者，但無法抑制殘留在腦部的死亡蟲體引起的免疫反應造成腦部的損傷。GM6001是一種間質蛋白分解酵素專一的抑制劑，其可螯合間質蛋白分解酵素作用時所必需的鋅離子，以阻礙酵素活性，之前的研究已知GM6001可阻斷白血球移行及抑制自體免疫疾患造成的腦膜腦炎。本研究的目標是評估Albendazole配合GM6001混合治療廣東住血蟲感染造成的腦膜炎之效果。Zymography的分析結果顯示GM6001可以抑制MMP-9的活性，經過混合治療後的小鼠腦脊髓液及腦組織的MMP-9與感染組相比活性明顯減少。感染廣東住血線蟲的小鼠發炎細胞明顯增加，經治療後則明顯減少。混合治療的蟲回收數明顯地較感染組較少。這些結果顯示廣東住血線蟲的感染，以MMP inhibitor治療寄生蟲引起腦膜炎是相當好的策略。而Albendazole配合GM6001的混合治療不但可以殺蟲，並可以減少腦部的發炎反應。我們的結論是以MMP inhibitor GM6001治療寄生蟲引起的腦膜炎有相當好的效益。 Matrix metalloproteinase 9 (MMP-9) is involved in the Angiostrongylus cantonensis infected meningitis. Recently, some effective anthelmintics have been proposed to treat the A. cantonensis in humans. But worm dead bodies leaving in the brain still evoke severe immune response resulting in brain damage. The MMP-specific inhibitor GM6001 acts by chelating the zinc cation in the active site of MMPs, in previous has been reported to block leukocyte migration and suppress autoimmune encephalomyelitis. In an attempt to prevent brain damage caused by worm migration and MMP-9 destruction during A. cantonensis infection, we were combine anthelmintic albendazole and MMP inhibitor GM6001 to kill worms and block MMP-9 activity, respectively. The aim of the present study was to estimate the efficacy of this combining therapy in parasitic meningitis caused by A. cantonensis infection. In a zymography assay GM6001 was able to inhibit MMP-9 activity, the activity in cerebrospinal fluid (CSF) and brain tissues were significantly decreased in combing treatment compared to infected mice with parasitic meningitis. Inflammatory cells were significant increased in infected-mice, and decreased the numbers after treatment. Recovered larvae in combing treatment were significantly decreased, compared to the infected mice. These data suggest that inhibition of MMP-9 may be an effective approach to prevent brain inflammatory reaction caused by A. cantonensis infection. Combing therapy with albendazole and GM6001 seem to be better agents to kill the worm and prevent brain damage. We conclude that an MMP inhibitor have a significant beneficial effect in parasitic meningitis.
