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目的:为增进对青蒿素作用机制的了解,探讨参与调节线粒体体积的线粒体通透性转移孔在青蒿素抗疟机制中的作用。方法:分离线粒体,采用分光光度法检测青蒿素能否直接作用于离体线粒体导致线粒体体积变化;利用等效应图分析线粒体通透性转移孔抑制剂是否拮抗青蒿素的抗疟作用。结果:青蒿素可以直接导致离体疟原虫线粒体肿胀,而不会影响鼠肝线粒体体积;两种不同的线粒体通透性转移孔抑制剂均可拮抗青蒿素的抑疟效果。结论:青蒿素可以直接作用于离体疟原虫线粒体导致线粒体肿胀,且青蒿素导致线粒体肿胀的物种选择性与细胞毒性的物种选择性一致。此外,利用抑制剂阻断线粒体通透性转移孔的开放可以拮抗青蒿素的抗疟效果,证明线粒体通透性转移孔在青蒿素抗疟过程中起重要作用。
OBJECTIVE: To improve the understanding of the mechanism of action of artemisinin, to explore the role of mitochondrial permeability transition pores involved in the regulation of artemisinin antimalarial mechanisms. METHODS: Mitochondria were isolated and spectrophotometric assay was used to determine whether artemisinin could directly affect mitochondrial volume changes induced by ex vivo mitochondria; isoimpedance plots were used to analyze whether mitochondrial permeability transition pore inhibitors antagonized the antimalarial effects of artemisinin. RESULTS: Artemisinin could directly lead to swelling of mitochondria isolated from Plasmodium vivax without affecting rat liver mitochondrial volume. Two different mitochondrial permeability transition pore inhibitors could antagonize the anti-malarial effect of artemisinin. Conclusion: Artemisinin can directly act on the mitochondria of isolated Plasmodium mitochondria to cause swelling of the mitochondria, and the artemisinin-induced mitochondrial swelling of the species selectivity is consistent with the species selectivity of cytotoxicity. In addition, the use of inhibitors to block the opening of mitochondrial permeability transition pores can antagonize the antimalarial effects of artemisinin, demonstrating that mitochondrial permeability transition pores play an important role in the artemisinin antimalaria process.