雷公藤内酯醇的遗传毒性评价
投稿时间:2015-11-15  修订日期:2016-01-14  点此下载全文
引用本文:田逸君,郑怡文,朱玉平,张晓芳,宗英,陆国才.雷公藤内酯醇的遗传毒性评价[J].药学实践杂志,2016,34(3):215~218
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作者单位E-mail
田逸君 第二军医大学卫生毒理学教研室, 上海 200433  
郑怡文 第二军医大学卫生毒理学教研室, 上海 200433  
朱玉平 第二军医大学卫生毒理学教研室, 上海 200433  
张晓芳 第二军医大学卫生毒理学教研室, 上海 200433  
宗英 第二军医大学卫生毒理学教研室, 上海 200433  
陆国才 第二军医大学卫生毒理学教研室, 上海 200433 newdrug@smmu.edu.cn 
基金项目:国家科技重大专项基金(2014ZX09J14106-06C,13CXZ005,BWS14J023);国家自然科学基金(81473291,81402651);上海市自然科学基金(13ZR144940)
中文摘要:目的 观察雷公藤的主要有效成分之一雷公藤内酯醇的遗传毒性。方法 采用鼠伤寒沙门氏菌回复突变试验(Ames试验)、体外培养CHO细胞染色体畸变试验和小鼠骨髓微核试验检测雷公藤内酯醇的遗传毒性。结果 Ames试验提示在每皿1.6~1000 μg受试剂量下,在加或不加S9代谢活化系统时,受试物对组氨酸缺陷型鼠伤寒沙门氏菌TA97、TA98、TA100、TA102及TA1535所诱发的回复突变菌落数均与溶媒对照的突变菌落数相近。体外培养CHO细胞染色体畸变试验结果显示0.01、0.02和0.04 μg/ml 3个剂量的受试物,对加与不加S9代谢活化系统培养的CHO细胞的染色体畸变率无明显影响。小鼠骨髓微核试验设180、360、720 μg/kg 3个剂量,在720 μg/kg剂量时,雷公藤内酯醇有诱发骨髓嗜多染红细胞微核率增高的效应。结论 在本实验条件下,雷公藤内酯醇对鼠伤寒沙门氏菌无致突变性,对哺乳动物培养细胞染色体无致畸变作用,720 μg/kg剂量下对ICR小鼠有诱发骨髓嗜多染红细胞微核率增高的效应。提示雷公藤内酯醇对人体可能具有潜在的遗传毒性。
中文关键词:雷公藤内酯醇  致突变试验  鼠伤寒沙门氏菌回复突变试验  染色体畸变试验  微核试验
 
Genotoxicity evaluation of triptolide
Abstract:Objective To study the genotoxicity of triptolide, an important active component of Tripterygium wilfordii Hook f. Methods Ames test, in vitro chromosomal aberration test of CHO cell and in vivo micronucleus assay were performed to investigate the genotoxicity of triptolide. Results The Ames test showed that triptolide did not increase mutagenicity for TA97, TA98, TA100, TA102 and TA1535 strains at the dosage of 1.6~1000 μg per plate with and without metabolic activation system S9. Results of in vitro CHO cell chromosomal aberration test indicated that there was no statistical difference between the triptolide groups (doses of 0.01, 0.02 and 0.04 μg/ml) and the solvent control group with and without metabolic activation system S9. However, triptolide significantly increased polychromatophilic erythrocyte micronucleus formation at the dosage of 720 μg/kg in ICR mice. Conclusion Triptolide did not induce genetic toxicity based on the Ames test and chromosomal aberration test, but could increase micronucleus formation at the dosage of 720 μg/kg. These results indicated that triptolide may have potential genotoxicity on human health.
keywords:triptolide  mutagenicity test  Ames test  chromosomal aberration test  micronucleus assay
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