Orjih A U
Department of Internal Medicine, St Louis University School of Medicine, Missouri, USA.
Br J Haematol. 1996 Feb;92(2):324-8. doi: 10.1046/j.1365-2141.1996.d01-1471.x.
This study has examined in vitro, how exposure to the antimalarial drug artemisinin affects Plasmodium falciparum and its host erythrocytes. Factors examined include: cell morphology, intracellular haemoglobin levels, and haemoglobin catabolism (haemozoin production). To avoid uninfected erythrocytes complicating the study, P. falciparum ring-infected erythrocytes were concentrated to 99% parasitaemia, by saponin haemolysis, before the parasites were grown with or without artemisinin. Without artemisinin, the parasites completed their life cycle in the normal time (40 h), during which a mean of 980 pmol if ferriprotoporphyrin IX from haemoglobin was incorporated into haemozion per 10(6) parasitized erythrocytes, and intracellular haemoglobin level decreased by 90%. Exposure of ring-infected erythrocytes to artemisinin (250 ng per ml of culture medium) inhibited parasite growth completely, haemozoin production by 95%, and decreased the intra-erythrocytic haemoglobin level by 90%; the infected erythrocytes remained intact during the 64 h of study. Haemozoin production was also inhibited when the drug was administered at the trophozoite stage of parasite growth, but the infected erythrocytes haemolysed. These findings may contribute to understanding of antimalarial actions of artemisinin that promote parasite clearance.
本研究在体外检测了接触抗疟药物青蒿素如何影响恶性疟原虫及其宿主红细胞。所检测的因素包括:细胞形态、细胞内血红蛋白水平以及血红蛋白分解代谢(疟色素生成)。为避免未感染的红细胞使研究复杂化,在用或不用青蒿素培养疟原虫之前,通过皂素溶血将感染恶性疟原虫环状体的红细胞浓缩至疟原虫血症水平为99%。在没有青蒿素的情况下,疟原虫在正常时间(40小时)内完成其生命周期,在此期间,每10⁶个被寄生的红细胞中平均有980皮摩尔来自血红蛋白的高铁原卟啉IX被整合到疟色素中,细胞内血红蛋白水平下降了90%。将感染环状体的红细胞暴露于青蒿素(每毫升培养基250纳克)中可完全抑制疟原虫生长,抑制疟色素生成95%,并使红细胞内血红蛋白水平下降90%;在64小时的研究过程中,被感染的红细胞保持完整。当在疟原虫生长的滋养体阶段给予该药物时,疟色素生成也受到抑制,但被感染的红细胞发生溶血。这些发现可能有助于理解青蒿素促进疟原虫清除的抗疟作用。