2026-11-092026-11-09https://scholars.csmu.edu.tw/handle/123456789/38616Toxoplasma gondii is an obligate intracellular protozoan parasite with a global distribution among humans and animals. Infection is normally controlled by the host immune system leading to an asymptomatic chronic stage of infection in which a balanced host–parasite interaction assures both survival of the host and maximum chance for transmission of the parasite. Matrix metalloproteinases (MMPs) were a family of zinc metallo-endopeptidases that regulate cell-matrix composition. The MMPs were produced as zymogens with a signal sequence and propeptide segment that must be removed during activation. Our previous study showed that MMP-9 may play a role in the pathogenesis of eosinophilic meningitis of angiostrongyliasis. To evaluate the proteolytic enzymes in genetically different strains of mice with toxoplasmosis, BALB/c (a toxoplasmosis resistant strain) and C57BL/6 (a toxoplasmosis susceptible strain) mice were infected with T. gondii oocysts orally and subsequently injected intraperitoneally with MMPs inhibitor. A possible role not only in host resistance but also in parasite-induced immune-mediated pathology, the MMPs from several T. gondii-resistant and -susceptible mice were compared. The mice infected with T. gondii induced-encephalitis as a model. The first year, we will investigate the mRNA expression of 28 MMPs, MMPs activity and localization in T. gondii-infected astroglia. The second year is to investigate the inhibited effect of MMPs inhibitor in T. gondii-infected astroglia. The third year is to reveal the differences of cysts and MMPs in BALB/c and C57BL/6 mice. The aim of the present study was to provide the clinical evaluation on the diagnosis and therapy efficacy of T. gondii-induced encephalitis.弓蟲(Toxoplasma gondii)是一種專性細胞內寄生的原蟲，此蟲能感染絕大部分的哺乳類動物，包括人。弓蟲症(Toxoplasmosis)的世界性分布，對人類健康與經濟動物的影響甚巨，過去弓蟲症在台灣的盛行率並不高，但由於國人飲食習慣逐漸改變傾向歐美化，感染弓蟲的機會因此提高，加上近年來愛滋病在台灣日趨嚴重，因此弓蟲症的研究在台灣日益重要。當宿主免疫系統健全時，可壓抑速殖子(tachyzoites)之繁殖，在中樞神經系統中會轉變為緩殖子(bradyzoites)或囊胞(cyst)。若宿主的免疫系統受到抑制，囊胞破裂釋放出緩殖子，會造成急性感染的復發。基質金屬蛋白酶(matrix metalloproteinases, MMPs)是一種含鋅的金屬酵素，以酵素原型態(proenzyme)產生，能分解細胞外質(extracellular matrix, ECM)。這些蛋白分解酶(proteolytic enzymes)在生理和病理方面對結締組織的重建佔有重要地位，就如同發炎反應的的調節器。本實驗室先前的研究顯示MMP-9酵素系統與嗜伊紅性腦膜炎(eosinophilic meningitis)有關，且可以做為廣東住血線蟲(Angiostrongylus cantonensis)引起腦膜炎的指標性酵素。過去很少研究報告探討弓蟲引起的腦炎與蛋白分解酵素的關係，本研究擬以對弓蟲較具感受性(a susceptible strain)的C57BL/6鼷鼠及較具抗性(a resistant strain)的BALB/c鼷鼠感染弓蟲，誘發腦炎的模式進行研究。第一年分析目前已發現的28種MMPs mRNA在星狀膠細胞感染弓蟲後之表現，並分析MMPs酵素活性及在細胞之定位。第二年以MMPs專一性的酵素抑制劑處理，評估酵素抑制劑對星狀膠細胞感染弓蟲後誘發之MMPs及細胞病癥之抑制作用。第三年比較C57BL/6鼷鼠及BALB/c鼷鼠腦組織中的囊體數，並分析弓蟲引起腦炎後MMPs的表現，進一步找出弓蟲感染時導致腦炎之致病機轉，由此模式提供臨床上診斷 及治療此症之參考。弓蟲基質金屬蛋白酶腦炎Toxoplasma gondiimatrix metalloproteinasesencephalitisProject