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氯喹对恶性疟原虫的体外阶段依赖性作用。

Stage-dependent effects of chloroquine on Plasmodium falciparum in vitro.

作者信息

Yayon A, Vande Waa J A, Yayon M, Geary T G, Jensen J B

出版信息

J Protozool. 1983 Nov;30(4):642-7. doi: 10.1111/j.1550-7408.1983.tb05336.x.

DOI:10.1111/j.1550-7408.1983.tb05336.x
PMID:6198514
Abstract

The erythrocytic developmental cycle of Plasmodium falciparum can be conveniently divided into the ring, trophozoite, and schizont stages based on morphology and metabolism. Using highly synchronous cultures of P. falciparum, considerable variation was demonstrated among these stages in sensitivity to chloroquine. The effects of timed, sequential exposure to several clinically relevant concentrations of chloroquine were monitored by three techniques: morphological analysis, changes in the rate of glucose consumption, and changes in the incorporation of 3H-hypoxanthine into parasite nucleic acids. All three techniques gave essentially identical results. The trophozoite and schizont stages were considerably more sensitive to the drug than ring-stage parasites. Chloroquine sensitivity decreased as nuclear division neared completion. The increase in chloroquine sensitivity was coincident with a marked rise in the rate of glucose consumption and nucleic acid synthesis. The rate of nucleic acid synthesis decreased as schizogony progressed while glucose consumption continued at high rates during this process. The degree of chloroquine sensitivity was not highly correlated with either metabolic activity.

摘要

恶性疟原虫的红细胞发育周期可根据形态和代谢方便地分为环状体、滋养体和裂殖体阶段。使用高度同步化的恶性疟原虫培养物,已证明这些阶段对氯喹的敏感性存在相当大的差异。通过三种技术监测了定时、顺序暴露于几种临床相关浓度氯喹的效果:形态学分析、葡萄糖消耗速率的变化以及3H-次黄嘌呤掺入寄生虫核酸的变化。这三种技术给出的结果基本相同。滋养体和裂殖体阶段对该药物的敏感性明显高于环状体阶段的寄生虫。随着核分裂接近完成,氯喹敏感性降低。氯喹敏感性的增加与葡萄糖消耗速率和核酸合成的显著升高同时发生。随着裂体增殖的进行,核酸合成速率下降,而在此过程中葡萄糖消耗继续以高速率进行。氯喹敏感性程度与任何一种代谢活性均无高度相关性。

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