青蒿琥酯对比格犬骨髓幼红细胞成熟的影响  

Effects of artesunate on maturation of erythroblasts in beagle dogs

作　　者：姚朗[1] 滕翕和[1] 熊春生[1] 

机构地区：[1]军事医学科学院微生物流行病研究所

出　　处：《中国药理学与毒理学杂志》1993年第3期231-234,共4页Chinese Journal of Pharmacology and Toxicology

摘　　要：为探讨青蒿素类药物引起骨髓红系前体细胞成熟障碍的毒性机理,本文研究了青蒿琥酯(Art)对血红素生物合成的影响。荧光分光光度法测定发现比格犬po Art后外周血红细胞游离原卟啉含量升高;铁染色显示用药犬外周血及骨髓出现铁粒幼细胞;电镜观察及X-射线微区元素分析表明,铁粒幼细胞线粒体沉积颗粒的主要元素为铁和磷,Art的上述毒性反应为可复性,不同剂量时呈现作用的复杂性。It has been shown that artesunate(Art),a derivative of antimalarial artemisinine,can inhibit the erythropoiesis in animal models.Considering that the biosynthesis of heme is one of the principal events in erythropoiesis,the authors studied the effects of Art on heme biosynthesis in beagles.By using the fluorospectrophotometric method,it was found that the content of peripheral free erythrocyte protoporphyrin(FEP)was significantly elevated in beagles orally administrated with Art 15 mg·kg-1·d-1 for consecutive 28 d.The FEP on d 28 was 4.41±s 0.58 mg·L-1RBC(n=6),which is 6.5 fold higher than that of the blank control group.The results of iron stain showed that there were many ring sideroblasts in the peripheral and marrow smears of 15 and 82.5 mg·kg-1·d-1 Art treated beagles.Underthe electron microscopy,some dense granules in the mitochondrial matrices of the sideroblasts were observed.By electron probe microanalysis,the essential elements of the granules were identified to be iron and phosphorus.The Fe/P intensity ratio was 1.48±s 0.19(n=12).The action of Art is reversible.All the results mentioned above suggest that Art can interfere with heme biosynthesis.The possibility that Art exerts the toxic effects by inhibiting the activity of mitochondrial ferrochelatase is discussed.

关 键 词：青蒿琥酯 血红素 原卟啉类 

分 类 号：R994.1[医药卫生—毒理学]