低浓度双氢青蒿素对恶性疟原虫3D7株干预效应观察

郭媛1 李凯2,3 姜晓慧2,3 杨婷1,2 郑钟原1,2 陈利娜2,3 李玉洁2,3 郑晓俊4

(1.山西医科大学药学院, 山西太原 030001)
(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。

【关键词】 双氢青蒿素; 恶性疟原虫; 红内期; 生长周期;

【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)

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This Article

ISSN:1001-5302

CN: 11-2272/R

Vol 43, No. 16, Pages 3397-3403

August 2018

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摘要

  • 1 材料
  • 2 方法
  • 3 结果
  • 4 讨论
  • 参考文献