孕前炔雌醇暴露对大鼠子代糖代谢变化和肝脏糖代谢相关基因表达的影响  

Pregestational ethinyl estradiol exposure leads to glucose homeostasis disruption and changes of expressions of glucose-metabolism-related genes in rat offsprings

作　　者：徐凯旋[1] 李宁宁[1] 管磊剑 夏彦恺[1] 吴笛[1] 

机构地区：[1]南京医科大学公共卫生学院卫生毒理学系,江苏南京211166

出　　处：《中国实验动物学报》2016年第3期221-227,共7页Acta Laboratorium Animalis Scientia Sinica

基　　金：国家自然科学基金资助项目(81470150);江苏省高校自然科学研究计划项目(12KJB330001);留学回国人员科研启动基金

摘　　要：目的以SD大鼠为模型,观察孕前炔雌醇(ethinyl estradiol,EE)暴露对子代糖代谢变化和肝脏内与糖代谢相关基因表达的影响。方法 52只雌性大鼠随机分为4组:对照组(芝麻油)、50、200、800μg/kg EE组,每天1次,连续灌胃暴露15 d后受孕。在子代出生后第23天(postnatal day,P23)和P25分别进行口服葡萄糖耐量(OGTT)和胰岛素耐量(ITT)实验,并用RT-PCR检测肝脏中糖代谢相关基因表达水平。结果子代雌鼠OGTT:200μg/kg EE组空腹血糖值显著低于对照组(P<0.05);800μg/kg EE组第15min血糖值显著高于对照组、50、200μg/kg EE组(P<0.01,P<0.01,P<0.01),50、800μg/kg EE组2 h血糖值显著低于对照组(P<0.05,P<0.01)。子代雄鼠OGTT:在第15 min,800μg/kg EE组血糖值显著高于对照组(P<0.01);第30 min时,200μg/kg EE组血糖值显著低于对照组(P<0.05)。子代雌鼠ITT:第15 min时,50、200μg/kg EE组血糖值显著高于对照组(P<0.001,P<0.01)。子代雄鼠ITT:第30 min时50、200μg/kg EE组血糖值显著高于对照组(P<0.01,P<0.01)。子代雌鼠RT-PCR:50,200μg/kg EE和800μg/kg EE组Glut2和Lpk mRNA表达水平显著低于对照组(P<0.01,P<0.05,P<0.05);50、200μg/kg EE组Gys2 mRNA表达水平显著低于对照组(P<0.01,P<0.01)。子代雄鼠RT-PCR:200μg/kg EE组G6pase和Pepck mRNA表达水平显著高于对照组(P<0.01,P<0.01),50μg/kg EE组Glut2 mRNA表达水平相对于对照组显著降低(P<0.01),800μg/kg EE组Gys2 mRNA表达水平显著高于对照组(P<0.01)。结论孕前炔雌醇暴露会导致子代雌鼠葡萄糖耐量受损、子代出现胰岛素抵抗及肝脏内糖代谢相关基因表达异常。而且这些效应具有性别差异,子代雌鼠对孕前EE暴露更敏感。Objective The aim of this study was to observe pregestational ethinyl estradiol（ EE）-exposure-induced glucose metabolism alterations and hepatic glucose-metabolism-related gene expression changes in the offsprings of SD rats. Methods Fifty-two female and 52 male SD rats were used in this study. The female rats were gavaged with sesame oil,50 μg / kg,200 μg / kg and 800 μg / kg EE for 15 consecutive days. After the end of exposure period,the female rats were mated with male rats and gave birth to next generation. The blood glucose and insulin tolerance in the offsprings were measured on postnatal days 23（ P23） and 25（ P25）. The expressions of hepatic glucose-metabolism-related genes were measured by RT-PCR. Results In the female offsprings,the 200 μg / kg EE group had significantly lower fasting blood glucose level than that in the control group（ P〈0. 05）. At 15 min after glucose administration,the blood glucose level in the 800 μg / kg EE group was much higher than that in the control group,50 μg / kg and 200 μg / kg EE groups（ P〈0. 01,P〈0. 01,P〈0. 01）. At the time point of 2 h,the blood glucose level of the 50 μg / kg and 800 μg / kg EE groups were both significantly lower than that in the control group（ P〈0. 05,P〈0. 01）. The female offsprings in the 50μg /kg and 200 μg /kg EE groups had significantly higher glucose level after insulin administration than that in the control group（ P〈0. 001,P〈0. 01）. In the male offsprings,the 800 μg / kg EE group had a significantly higher blood glucose level than the control group at 15 min after glucose administration（ P〈0. 01）,and the 200 μg / kg EE group had a lower blood glucose level than the control at 30 min after glucose administration. In the male offsprings,the blood glucose level of50 μg / kg and 200 μg / kg EE groups were much higher than that of the control group（ P〈0. 01,P〈0. 01）. In the female offsprings,Glut2 and Lpk mRNA expressions in the 50 μg / kg,200 μg / kg and 800 μg / kg EE grou

关 键 词：孕前 炔雌醇 糖代谢失衡 肝脏 

分 类 号：Q95-33[生物学—动物学]