青蒿琥酯诱发大鼠骨髓红细胞微核

Induction of micronuclei in rat bone marrow erythrocytes by sodium artesunate

青蒿琥酯是新抗疟药青蒿素的水溶性衍生物。本实验通过大鼠骨髓微核试验对其遗传学毒性进行了研究。结果表明，青蒿琥酯 １００～３００ｍｇ／ｋｇ单次尾静脉注射后６ ｈ均诱发早期微核，并与剂量呈正相关。青蒿琥酯 ４８和 ９６ ｍｇ／ ｋｇ（分别相当于临床剂量的２０和４０倍）给药后６、１２、２４ ｈ引起骨髓多染红细胞（ＰＣＥ）微核频率增高，ＰＣＥ／ＮＣＥ（正成红细胞）比率下降， ２４ｍｇ／ｋｇ（临床剂量的 １０倍）对微核率及ＰＣＥ／ ＮＣＥ比率均未见明显改变。结果提示，高剂量青蒿琥酯不仅可引起大鼠骨髓红系造血抑制，而且可能引起遗传学毒性。

The genetic toxicity of sodium artesunate(SA), a water soluble derivative of the new antimalarial drug-artemisine was studied with in vivo rat micronucleus assay. A dose-related increase of micronucleated PCE was found as early as 6 hours after a single tv SA(100-300 mg / kg). An increased micronucleated PCE and decreased ratio of PCE to NCE were also detected at 6, 12 and 24 hours after 48 and 96 mg / kg SA treatment (equal to 20 and 40 times of the clinical dose respectively). However, no genetic and hematopoietic effects were found in the low dose group. These results seem to indicate that SA may not only be hematotoxic but also genetoxic in rat bone marrow erythrocytes at the high dose level.