磷酸萘酚喹对循环中的环状期疟原虫具有快速清除作用的机制
A Basis for Rapid Clearance of Circulating Ring-Stage Malaria Parasites by the Spiroindolone KAE609.
作者信息
Zhang Rou, Suwanarusk Rossarin, Malleret Benoit, Cooke Brian M, Nosten Francois, Lau Yee-Ling, Dao Ming, Lim Chwee Teck, Renia Laurent, Tan Kevin Shyong Wei, Russell Bruce
机构信息
Department of Microbiology, Yong Loo Lin School of Medicine.
Singapore Immunology Network (SIgN), Agency for Science Technology and Research (A*STAR), Biopolis.
出版信息
J Infect Dis. 2016 Jan 1;213(1):100-4. doi: 10.1093/infdis/jiv358. Epub 2015 Jul 1.
Recent clinical trials revealed a surprisingly rapid clearance of red blood cells (RBCs) infected with malaria parasites by the spiroindolone KAE609. Here, we show that ring-stage parasite-infected RBCs exposed to KAE609 become spherical and rigid, probably through osmotic dysregulation consequent to the disruption of the parasite's sodium efflux pump (adenosine triphosphate 4). We also show that this peculiar drug effect is likely to cause accelerated splenic clearance of the rheologically impaired Plasmodium vivax- and Plasmodium falciparum-infected RBCs.
近期的临床试验显示，螺吲哚酮KAE609能惊人地快速清除感染疟原虫的红细胞（RBC）。在此，我们表明，暴露于KAE609的环状体期寄生虫感染的红细胞会变成球形且僵硬，这可能是由于寄生虫的钠外流泵（三磷酸腺苷4）被破坏导致渗透调节失调所致。我们还表明，这种特殊的药物作用可能会导致感染间日疟原虫和恶性疟原虫的红细胞因流变学受损而加速被脾脏清除。
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