| 益母草碱对胚胎-胎仔发育毒性和遗传毒性的评价 |
| 投稿时间：2020-04-21 修订日期：2020-06-28 点此下载全文 |
| 引用本文：田逸君,朱玉平,马玺里,严朗,勝呂綸貴子,郑怡文.益母草碱对胚胎-胎仔发育毒性和遗传毒性的评价[J].药学实践杂志,2020,38(5):451~457 |
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| 中文摘要:目的 检测益母草碱的发育毒性和遗传毒性。方法 在SD孕鼠妊娠第6~15天经口灌胃给予500、1 000和2 000 mg/kg体重的益母草碱，同时设溶媒对照组，经口灌胃0.5% CMC-Na溶液。妊娠第20天剖杀孕鼠，分析其生殖毒性。分别采用反映基因突变的鼠伤寒沙门菌回复突变试验（Ames试验）、反映染色体畸变的细胞染色体畸变试验（体外培养CHO）和ICR小鼠骨髓微核试验（体内）检测益母草碱的遗传毒性。结果 在500、1 000和2 000 mg/kg剂量益母草碱的作用下孕鼠的增重与对照组相比，差异均无统计学意义；各受试剂量组孕鼠各项指标与对照组相比，差异均无统计学意义；各剂量组胎鼠各类指标与溶媒对照组相比，无明显差异。Ames试验结果提示：在0.5、5、50、500、5 000 μg/皿受试剂量下，在有或无代谢活化S9系统时，与溶媒对照组相比，受试物对组氨酸缺陷型鼠伤寒沙门菌（TA97、TA98、TA100、TA102及TA1535）所诱发的回复突变菌落数均相近。染色体畸变试验结果显示：250、500和1 000 μg/ml 3个剂量的受试物，对有或无代谢活化系统S9培养的CHO细胞的染色体畸变率无明显影响。微核试验显示100、500和2 000 mg/kg各个剂量组对ICR小鼠的微核诱发率与溶媒对照组比较均无显著差异（P>0.05）。结论 益母草碱在500、1 000和2 000 mg/kg剂量下未观察到明显的母体毒性、胚胎毒性、胎儿毒性和致畸作用。益母草碱对鼠伤寒沙门菌无致突变性，对哺乳动物培养细胞的染色体无致畸变作用，对ICR小鼠无诱发骨髓嗜多染红细胞微核的效应。上述结果表明在本试验条件下，益母草碱无发育和遗传毒性。 |
| 中文关键词:益母草碱 发育毒性 遗传毒性 |
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| Evaluation for embryo-fetal developmental toxicity and genetic toxicity of leonurine |
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| Abstract:Objective To evaluate the developmental toxicity and genotoxicity of leonurine.Methods Leonurine was given orally to SD pregnant rats on the 6th to 15th day of pregnancy at the dose of 500, 1 000 and 2 000 mg/kg body weight. The control group received 0.5% CMC-Na solution orally. Pregnant rats were sacrificed on the 20th day of pregnancy to analyze the reproductive toxicity. Ames test, in vitro chromosomal aberration test of CHO cell and in vivo micronucleus assay were performed to investigate the genotoxicity of leonurine.Results There was no difference statistically in weight gain of pregnant mice between two groups at the dose of 500, 1 000 and 2 000 mg/kg of motherwort alkaloids. In vitro CHO cell chromosomal aberration test indicated that there was no statistical difference between leonurine groups (doses of 250, 500 and 1 000 μg/ml) and the solvent control group with and without metabolic activation system S9. The number of micronuclei in ICR mice did not increase (P>0.05) in the mouse bone marrow micronucleus test at the doses of 100, 500 and 2 000 mg/kg.Conclusion No significant maternal toxicity, embryo toxicity, fetal toxicity and teratogenic effects were observed with leonurine at 500, 1 000 and 2 000 mg/kg doses. Leonurine was not genotoxic in Salmonella typhimurium reverse mutation test, in vitro CHO cells chromosome aberration test or mouse bone marrow micronucleus test. It showed that leonurine had no developmental toxicity and genotoxicity under the conditions of the experiment. |
| keywords:leonurine developmental toxicity genotoxicity |
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