雄黄与砷甲基化代谢物遗传毒性的比较研究  

Comparative Study on the Genotoxicity of Realgar and Arsenic Methylated metabolites

作　　者：钱勤 王子妤[1] 卞倩[2] 刘德晔[2] 李伟[1] 董菊[1] 李国春[1] Qian Qin;Wang Ziyu;Bian Qian;Liu Deye;Li Wei;Dong Ju;Li Guochun(School of Medicine&Holistic Integrative Medicine,Nanjing University of traditional Chinese medicine,Nanjing 210035;Jiangsu Provincial Center for Disease Control and prevention,Nanjing 210009)

机构地区：[1]南京中医药大学医学院·整合医学学院,南京210035 [2]江苏省疾病预防控制中心,南京210009

出　　处：《中药药理与临床》2021年第2期65-68,共4页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金项目资助(编号:81774025)。

摘　　要：目的:检测并比较雄黄与四种甲基化代谢物(MMAⅢ、DMAⅢ、MMAⅤ及DMAⅤ)遗传毒性大小。方法:以CHL细胞为研究对象,对雄黄浸出液和四种甲基化代谢物开展细胞毒性试验确定各自的IC50;各物质统一以1/4 IC50为剂量标准,开展染色体畸变实验、微核实验、单细胞凝胶电泳实验,进行遗传毒性的检测与比较。结果:各物质在1/4 IC50给药剂量下,雄黄浸出液染色体畸变率为7.5%,MMAⅢ和DMAⅢ畸变率分别是10%和14%,而MMAⅤ和DMAⅤ畸变率在5%~10%之间;雄黄浸出液与四种甲基化代谢物均能引起CHL细胞微核率增加,且除雄黄浸出液外,四种甲基化代谢物与空白对照组比较差异均有统计学意义(P<0.01);各物质均能引起CHL细胞的彗星尾长、Olive尾距、尾DNA%增加(P<0.05),且MMAⅢ和DMAⅢ组的上述三个观察指标较雄黄浸出液组明显升高(P<0.05)。结论:雄黄浸出液的遗传毒性明显低于MMAⅢ和DMAⅢ,但与MMAⅤ和DMAⅤ相比未见显著差异。Objective: To detect and compare the genotoxicities of Realgar and its methylated metabolites(MMAⅢ, DMAⅢ, MMAⅤand DMAⅤ). Methods: CHL cells were selected as the research object, cytotoxic experiments were carried out to determine the IC50 of realgar extract and its four methylated metabolites. Then 1/4IC50 was taken as the same intervention dose, the chromosome aberration experiment, micronucleus assay and Single cell gel electrophoresis experiment were done to detect and compare the genotoxicity of each substance. Results:When 1/4IC50 were taken as the intervention dose, the chromosomal aberration rate of realgar extract was 7.5%, and those of MMAⅢ and DMAⅢ were 10% and 14%,respectively, while those of MMAⅤ and DMAⅤ were 5%~10%. For realgar extract and the four methylated metabolites, the micronucleus rates of CHL cells were increased, while compared with the negative control group, there were the statistic significance for four methylated metabolites(P<0.01). The comet tail length, Olive tail moment and tail DNA% were increased by all the substances(P<0.05), compared with realgar extract group, the indexes in MMAⅢ and DMAⅢgroups were significantly increased(P<0.05)Conclusion: The genotoxicity of realgar extract is weaker than those of MMAⅢ and DMAⅢ, but there are no significant differences between realgar extract and MMAⅤ and DMAⅤ respectively.

关 键 词：雄黄 甲基化代谢物 遗传毒性 比较研究 

分 类 号：R285.1[医药卫生—中药学]