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[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。
[Objective] The research aimed to study the blocking effect of antisense oligodeoxyribonucleotides (ODN) on the expression of histidine rich protein (HRP) Ⅱ and HRP Ⅲ in Plasmodium falciparum and explore the new anti-malarial approach. [Method] The antisense ODN, sense ODN and nonsense ODN of the plasmodium falciparum histidine-rich protein translation region were designed and synthesized. The inhibitory effect on the proliferation and maturation of Plasmodium falciparum in red-phase was studied. [Result] Antisense ODN, sense ODN and nonsense ODN all inhibited the proliferation and maturation of P. falciparum when the concentration of ODN was higher than 1 μmol L, that is, ODN showed nonspecific inhibition of P. falciparum. Antisense ODN significantly inhibited the proliferation and schizonts maturation of P. falciparum cultured in vitro (P <0.01) when the concentration of ODN was in the range of 0 0 1 ~ 0 5 μmol L compared with the non-sense ODN control group The higher the ODN concentration, the greater the inhibitory effect. The inhibitory effect of ODN on the parasites had no significant difference compared with the non-ODN (P> 0.05). [Conclusion] Antisense ODN of HRP Ⅱ and HRP Ⅲ gene can inhibit the proliferation and maturation of Plasmodium falciparum by blocking the gene expression.