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  • 學位論文

弓蟲感染星狀膠細胞誘發基質金屬蛋白酶-12增加及彈性蛋白降解

Matrix metalloproteinase-12 increase and elastin degradation in astroglia infected with Toxoplasma gondii

指導教授 : 蔡崇弘 賴世展

摘要


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。當弓蟲感染宿主後常誘發弓蟲性腦炎(toxoplasmic encephalitis)。本研究我們利用弓蟲速殖子(TS-4 strain)感染星狀膠細胞(astroglia)的細胞模式進行研究,探討基質金屬蛋白酶-12(matrix metalloproteinase-12, MMP-12)和其受質彈性蛋白(elastin)的變化之致病機轉。結果顯示在感染組細胞培養液中發現MMP-12蛋白表現量在感染後第24小時和第48小時開始有明顯的增加。同樣的,彈性蛋白表現量在相同時間點也有顯著的增加。抑制組的星狀膠細胞於感染後分別加入0.01mM、0.1mM、0.5mM和1mM等四種不同濃度的MMPs專一酵素抑制劑GM6001共同培養。結果顯示0.5mM及1mM 等兩種濃度,細胞崩解的程度及MMP-12和彈性蛋白的蛋白表現量相較於感染組也有明顯的降低。試驗結果顯示在弓蟲感染星狀膠細胞的發展過程中,MMP-12扮演降解彈性蛋白的角色。

並列摘要


Toxoplasma gondii is an obligate intracellular protozoa in the mammal animals, including human. The host infected with T. gondii wich can induce toxoplasmic encephalitis. In this study, astroglia infected with TS-4 strain T. gondii tachyzoite and to investigate the changes of matrix metalloproteinase-12 (MMP-12) and its substrate elastin in the pathogenesis. The results showed that MMP-12 was found in the cell clutered medium of T. gondii infected-astroglia and significantly increased at 24hrs and 48 hrs post-infection (PI). Similarly, the expression of elastin was also increased at the same time points. The inhibitory test of astroglia infected with T. gondii was co-cultured with four different concentrations of MMPs inhibitor GM6001 (0.01mM, 0.1mM, 0.5mM and 1mM). The concentrations of GM6001 on 0.5mM and 1mM were significantly reduced the astroglia degradation, and the expression of MMP-12 and elastin in astroglia infected with T. gondii. These results suggested that MMP-12 may contribute to elastin degradation occurring in astroglia infected with T. gondii.

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