青蒿素与疟疾:药物激活、作用机理及抗药性的研究进展  

Artemisinin and malaria: Current understandings of drug activation, action, and resistance

作　　者：苏新专[1,2] 李剑[2] SU XinZhuan LI Jian(Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda 20892, USA State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen 361005, China)

机构地区：[1]Laboratory of Malaria and Vector Research,National Institute of Allergy and Infectious Diseases,National Institutes of Health [2]厦门大学生命科学学院,细胞应急生物学国家重点实验室,细胞信号网络协同创新中心,厦门361005

出　　处：《科学通报》2017年第18期1928-1937,共10页Chinese Science Bulletin

基　　金：国家自然科学基金(81220108019;81572017);国家外国专家局和教育部"111计划"(B06016);美国国家过敏和传染病研究所项目资助

摘　　要：如能及早确诊并合理救治,疟疾是可以通过抗疟药来治愈的.然而,抗药性疟原虫通常在一种新型药物的大规模使用后的数年内就会出现.随着疟原虫几乎对所有类型的抗疟药均产生了不同程度的抗性,青蒿素类药物联合疗法(ACTs)也由此成为治疗疟疾最重要的手段.不幸的是,已有报道称在东南亚地区采用青蒿素或ACTs治疗后出现了延迟原虫清除的现象,这也让研究者们对青蒿素及其衍生物治疗在未来发生完全失效的可能感到担忧.本文简要综述了青蒿素的药物激活、作用机理、药物靶点及可能的抗药性机制等研究的进展;对抗药性的定义、青蒿素组合用药中伴侣药物的选择,以及当前为消除疟疾采取全民用药的努力等问题作了讨论.与此相关的议题已有大量的研究和文献报道,由于篇幅有限未能逐一列举.此外,本文所讨论的某些问题仍存争议、还需深入的研究方能解答.Malaria is a disease that can be cured with antimalarial drugs if treated early and appropriately. However, parasites resistant to a new drug generally emerge within a few years after large-scale applications. Artemisinin（ART or Qinghaosu） combination therapies（ACTs） have become the major treatments for malaria after the emergence of parasites resistant to almost all classes of antimalarial drugs. Parasites with delayed parasite clearance（DPC） after ART or ACT therapies have also been reported in Southeast Asia, raising concerns of total failure of ART and its derivatives. Many classes of antimalarial drugs have been introduced to successfully treat malaria infections, including chloroquine, piperaquine, primaquine, mefloquine（MQ）, pyrimethamine, sulfadoxine, ART and derivatives, etc. Regrettably, many of these drugs have been abandoned by many countries in malaria endemic regions due to the emergence of drug resistant parasites. According to World Health Organization, parasite responses to a drug can be classified into four categories（S, RI, RII, and RIII）： Sensitivity（S） to a drug is defined as clearance of asexual parasitemia within seven days of the first day of treatment without recrudescence; Resistance RI is defined as clearance of asexual parasitemia as in sensitive parasites, followed by recrudescence; RII resistance is indicated by marked reduction of asexual parasitemia, but no clearance; and RIII resistance shows no marked reduction of asexual parasitemia. Currently, RII and RIII resistance to chloroquine, pyrimethamine, and other drugs have been widely reported; but residence to ART remains largely at R1 level. ART resistance was initially defined as parasites with half parasite clearance time（PC1/2）5 h under a standard ART treatment regimen（three-day artesunate treatment at 2–4 mg kg-1 d-1）. A second measurement is in vitro ring survival assay（RSA） that was developed based on the observation that the ring stages of some parasite strains could survive a short p

关 键 词：青蒿素 疟原虫 组合药物 全民用药 青蒿素类药物联合疗法 

分 类 号：R978.6[医药卫生—药品]