(2.中国中医科学院青蒿素研究中心, 北京 100700)
(3.中国中医科学院中药研究所, 北京 100700)
(4.山西医科大学第一医院药学部, 山西太原 030001)
【摘要】疟疾仍是严重威胁人类健康和生命安全的重大传染病, 非洲儿童死亡的头号杀手。既往研究表明, 青蒿素类药物可选择性杀灭红内期疟原虫, 且对环期影响较大。近年来其作用机制研究屡有新的发现, 但这些研究中采用的青蒿素类药物的浓度可达体外实验半数抑制浓度的50~80倍。该实验采用恶性疟原虫国际标准株3D7体外培养, 观察半数抑制浓度双氢青蒿素处置后, 恶性疟原虫红内期形态特征的变化, 进而探讨双氢青蒿素对3D7红内期生长周期及不同发育阶段的影响。恶性疟原虫3D7株进行连续同步化3次以上, 于末次同步化后6 h给予双氢青蒿素 (dihydroartemisinin, DHA) 半数抑制浓度 (10nmol·L-1) 1次, 连续观察3个生长周期 (132 h) 。研究结果显示, 与对照组相比, 双氢青蒿素作用后, 3D7生长显著抑制 (P<0.001) , 环状体生成率显著降低 (P<0.05) , 滋养体形态异常且不饱满, 裂殖体内裂殖子数量显著减少 (P<0.05) , 生长周期迟滞且紊乱。实验表明非杀灭浓度DHA可明显抑制恶性疟原虫的生长, 对3D7的干预效应可能不止作用于环期, 而是对疟原虫生长的各个环节均产生不同程度的影响。
【基金资助】 国家自然科学基金特别项目 (81641002) ; 中国中医科学院“十三五”重点领域项目 (Z2017021) ; 国家“重大新药创制”科技重大专项 (2017ZX09101002) ;
Effect of dihydroartemisinin at low concentration on intervention of Plasmodium falciparum 3D7 strain
(2.Research Center of Artemisinin, China Academy of Chinese Medical Sciences, Beijing, China 100700)
(3.Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China 100700)
(4.Pharmacy Department, First Hospital of Shanxi Medical University, Taiyuan, China 030001)
【Abstract】Malaria is an infectious disease affecting humans especially for children in tropical Africa. Previous studies have shown that artemisinin and its derivatives could selectively kill erythrocytic stage of malaria parasite and have a greater impact on the ring stage. In recent years, there have been new findings of its mechanism. However, the concentrations of artemisinin and its derivatives used in these studies can reach 50 to 80 times the half-inhibitory concentration in vitro. In this study, the international standard strain 3D7 of Plasmodium falciparum was cultured in vitro. After the strain was treated with half-inhibitory concentration of dihydroartemisinin (DHA), the morphological changes of intraerythrocytic P. falciparum were observed, and then the 3D7 life cycle and effects of DHA on this strain at different developmental stages were explored. The 3D7 strain of P. falciparum was continuously synchronised for more than three times, and DHA at half maximal inhibitory concentration (10 nmol·L−1) was administered for 6 h after the last synchronization, and three life cycles were continuously observed (132 h). The results showed that compared with the parasites untreated by DHA, there was a noticeable delay in the life cycle of at least 36 h, indicating that the growth of 3D7 was significantly inhibited by DHA (P < 0.001), and the rate of ring formation was significantly reduced (P < 0.05). The trophozoites were abnormal in shape, such as shrink in size, and the number of merozoites in schizonts was significantly decreased (P < 0.05). These results suggest that non-killing (meaning parasites can be inhibited but not killed) concentration of DHA can significantly inhibit the growth of P. falciparum, which may not only affect the ring stage, but also have an impact on other stages of P. falciparum.
【Keywords】 dihydroartemisinin; Plasmodium falciparum; erythrocytic stage of malaria; life cycle;
【Funds】 National Natural Science Foundation of China (81641002); Key Project of China Academy of Chinese Medical Sciences during the 13th Five-Year Plan of China (Z2017021); National Major Scientific and Technological Special Project for “Significant New Drugs Development” (2017ZX09101002);
 World Health Organization. World malaria report 2017 [R]. Geneva: World Healty Organization, 2017.
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