线粒体通透性转移孔与青蒿素抗疟机制研究

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.

Effect of mitochondrial permeability transition pore in antimalarial action of artemisinin

Objective:To promote understanding of the antimalarial mechanism of artemisinin and investigate the role of mitochondrial permeability transition pore,a protein complex which is involved in regulation of mitochondrial volume,in the antimalarial action of artemisinin. Methods:Mitochondria fraction was isolated from malaria parasites and mouse liver. Spectrophotometry was used to check the direct effect of artemisinin on the mitochondrial volume. Isobologram and inhibitors of mitochondrial permeability transi...