妊娠期使用司他夫定对ICR母鼠和子鼠肝细胞线粒体DNA D Loop的影响  

Effects of stavudine on the mitochondrial DNA D loop of hepatocytes in pregnant ICR mice and fetuses

作　　者：吴亚松[1] 石英[2] 柳雅立[2] 陈德喜[2] 张福杰[1,3] 吴昊[2] 

机构地区：[1]中国疾病预防控制中心性病艾滋病预防控制中心,北京102206 [2]首都医科大学附属北京佑安医院 [3]北京地坛医院

出　　处：《中国病原生物学杂志》2010年第11期801-804,共4页Journal of Pathogen Biology

基　　金："973"计划项目(No.2006CB504201)

摘　　要：目的研究ICR小鼠妊娠期使用司他夫定(d4T)后对亲代和子代小鼠肝脏线粒体DNA D loop区序列的影响。方法 20只ICR雌性小鼠分为2组,每组10只,从妊娠期第1 d起,每天分别以d4T 20 mg/kg和10 mg/kg灌胃至分娩。分娩后处死母鼠和子鼠,取肝脏,提取DNA,PCR扩增线粒体DNA D Loop区494 bp片段并测序,与参考序列(ref|NC_005089.1)比对,观察序列有无变化。结果母鼠和子鼠肝细胞线粒体DNA的D loop区序列未检测到突变位点。结论妊娠期使用人类相当治疗剂量的d4T不会导致小鼠肝脏细胞线粒体DNA D loop序列突变增加。d4T对线粒体DNA的影响需要进一步研究。Objective To evaluate the effects of stavudine（d4T） on the sequence of the mitochondrial DNA D loop in ICR mice.Methods Twenty pregnant ICR mice were divided into two groups and orally administered 10 and 20 mg·kg-1 of d4T daily,respectively,during the gestational period.The mother and neonates were sacrificed after delivery,and DNA was extracted from the liver.Fragments of the 494 bp mtDNA D loop were amplified by standard PCR.Direct DNA-sequencing analysis techniques were used to detect mitochondrial sequence variants.Alterations were determined by comparing the sequence to a reference sequence（ref｜NC_005089.1）.Results There were no nucleotide mutations in the mitochondrial DNA D loop in any of the ICR mice.Conclusion d4T did not induce mtDNA D loop mutations in hepatocytes of pregnant ICR mice and their fetuses when given during pregnancy in doses equivalent to a human dose.More comprehensive studies should be developed.

关 键 词：司他夫定 线粒体DNA ICR小鼠 

分 类 号：R392.1[医药卫生—免疫学]