中国寄生虫学与寄生虫病杂志 ›› 2000, Vol. 18 ›› Issue (4): 3-203.

• 论著 • 上一篇    下一篇

恶性疟原虫:组氨酸富集蛋白基因反义寡脱氧核苷酸体外抗疟作用初步研究

余新炳;方建民;罗树红
  

  1. 中山医科大学寄生虫学教研室!广东广州510089
  • 收稿日期:1900-01-01 修回日期:1900-01-01 出版日期:2000-08-30 发布日期:2000-08-30

PLASMODIUM FALCIPARUM : ANTIMALARIAL ACTIVITIES OF ANTISENSE OLIGODEOXYRIBONUCLEOTIDES TARGETED TO HISTIDINE-RICH PROTEIN GENES IN VITRO

YU Xin-bing;FANG Jian-min;LUO Shu-hong   

  1. Department of Parasitology;Sun Yat-sen University of Medical Sciences;Guangzhou 510089
  • Received:1900-01-01 Revised:1900-01-01 Online:2000-08-30 Published:2000-08-30

摘要:   [目的 ]研究反义寡脱氧核苷酸 (oligodeoxyribonucleotides,ODN)对恶性疟原虫组氨酸富集蛋白 (histidine richprotein ,HRP)Ⅱ和HRPⅢ基因表达的阻断作用 ,探讨抗疟新途径。 [方法 ]设计合成恶性疟原虫组氨酸富集蛋白翻译起始区的反义ODN、正义ODN和无义ODN ,研究其对红内期培养恶性疟原虫增殖和成熟的体外抑制作用。[结果 ]当ODN浓度较高时 (高于 1μmol L) ,反义ODN、正义ODN和无义ODN均能抑制恶性疟原虫的增殖和成熟 ,即ODN对疟原虫呈非特异性抑制。当ODN浓度在 0 0 1~ 0 5 μmol L时 ,与无义ODN对照组相比 ,反义ODN能显著抑制体外培养恶性疟原虫的增殖和裂殖体成熟 (P <0 0 1) ;且ODN浓度越高 ,抑制作用也就越强。正义ODN对虫体的抑制作用 ,与无义ODN相比其差异无显著性意义 (P >0 0 5 )。 [结论 ]HRPⅡ和HRPⅢ基因反义ODN可通过阻断基因的表达 ,抑制恶性疟原虫增殖和成熟的作用。

关键词: 寡脱氧核苷酸, 反义, 恶性疟原虫, 组氨酸富集蛋白, 疟色素

Abstract:  Objective] To study the inhibition of growth of Plasmodium falciparum cultured in vitro with antisense oligodeoxyribonucleotide (AS ODN) against histidine-rich proteins (HRP). [Methods] The ODNs against HRP Ⅱ and HRP Ⅲ were synthesized and used to study the antimalarial activities in vitro . Plasmodium falciparum (FCC1/HN strain, China) were exposed to AS DONs for 48 h, and the growth inhibi tion was determined by microscopic examination. [Results] At 1 μmol/L, all ODNs inhibited parasite growth and development in a target-indepentent manner. However, when the ODN concentrations were between 0.01 and 0 5 μmol/L, the AS ODN significantly inhibited the growth and development of P falciparum compared with ODN controls ( P <0 01). Inhibition by the sense strand ODN did not differ significantly from the control group ( P> 0 05). [Conclusion] Blockade of the expression of HRPⅡ and HRPⅢ AS ODN could inhibit P falciparum cultured in vitro .

Key words: oligodeoxyribonucleotide(ODN), antisense, Plasmodium falciparum histidine-rich protein (HRP), malarial pigment