青蒿琥酯诱发的自由基对孕鼠与胎鼠造血细胞的毒性

采用妊娠d 13-14 AMS小鼠骨髓和胎肝细胞微核和染色体畸变分析的联合试验方法观察青蒿琥酯对造血细胞的毒性, 并用电子自旋共振技术测定孕鼠和胚胎肝内自由基. 结果表明, 青蒿琥酯不但能诱发孕鼠骨髓细胞微核, 抑制骨髓造血, 而且能通过胎盘屏障损伤胎肝有核细胞. 但未发现对孕鼠骨髓和胎肝细胞的致染色体畸变作用. 青蒿琥酯给药能诱发孕鼠肝和胎肝内自由基信号增强. 本结果提示, 青蒿琥酯诱发经胎盘转运造血母细胞核质损伤和造血抑制可能与药物在体内形成的自由基有关.

Hemopoietotoxicity in pregnant mice and their embryos induced by free radicals derived from sodium artesunate

The hemopoietotoxic effects of artesunate (Art) on pregnant mice and their fetus have been studied with micronucleus assay and chromosome aberration analysis in combination. Mice of Academy of Military Medical Sciences strain were treated on d 13 or 14 of gestation with 40, 80, and 160 mg·kg^-1 Art intraperitoneally. Electron spin resonance technique was used to detect the free radicals both in maternal and fetal livers. The results showed that Art induced micronuclei and inhibited hemopoiesis not only in maternal bone marrow, but also in embryo liver erythro- blasts. Chromosome aberration was found neither in maternal nor in embryo hemopoietic cells even after treatment with high dose of 160 mg·kg^-1. It suggested that Art did not damage the chromosome directly. The possible mechanism of hemopoietotoxic effects was discussed.