尼古丁暴露孕鼠血代谢组学研究  

Study on maternal blood metabonomics in pregnant rats exposed to nicotine

作　　者：范杰[1] 鄢友娥[1] 刘岩松[1] 黄晶[1] 胡洁琼[1] 汪晖[1] 

机构地区：[1]武汉大学基础医学院药理学系,湖北武汉430071

出　　处：《环境与健康杂志》2015年第11期948-952,F0003,共6页Journal of Environment and Health

基　　金：国家自然科学基金(81430089);国家自然科学基金(81270950)

摘　　要：目的研究尼古丁暴露孕鼠外周血代谢物改变特征,寻找可能反映胎鼠发育异常的早期特征性代谢物。方法将Wistar孕鼠16只分为空白对照组和尼古丁处理组,于孕9~20 d分别皮下注射生理盐水和尼古丁[2 mg/（kg·d）],观察孕鼠体重变化,并分析不同时间点（孕11、14、17、20 d）血浆1H NMR代谢谱改变。结果尼古丁处理后孕鼠体重增长减慢,孕20 d体重低于对照组（P〈0.01）。孕鼠血浆糖、脂和蛋白质代谢相关的多种物质发生改变,孕14 d为重要变化时间点。孕11~14 d血浆中柠檬酸、甘油、N-乙酰糖蛋白、缬氨酸、亮氨酸、色氨酸、赖氨酸、异亮氨酸、不饱和脂肪酸、低密度脂蛋白胆固醇、尿囊素浓度升高（P〈0.05）,而丙酮酸、β-羟丁酸、肌醇浓度降低（P〈0.05）。结论 NMR代谢组学可作为孕鼠代谢改变检测的技术手段,β-羟丁酸、丙酮酸、柠檬酸、不饱和脂肪酸、甘油、缬氨酸、亮氨酸可能作为母体外周血中反映胎儿发育异常的早期特征代谢物。Objective To study the blood metabonomic alterations in pregnant rats exposed to nicotine, searching for characteristic metabolites from maternal blood served to alert abnormal fetal development. Methods Sixteen pregnant Wistar rats were randomly divided into normal control and nicotine-treated group（n=8）, pregnant rats were subcutaneous administered with nicotine [2 mg/（kg·d）] or saline from gestational day（GD） 9 to GD20. The body weight were recorded and metabonomes of maternal plasma on GD 11, 14, 17 and 20 were analyzed by1 H nuclear magnetic resonance（NMR） spectroscopy. Results Body weight gain of nicotine-exposed pregnant rats was slower than that of control group, and body weight on GD 20 in nicotine group was significantly decreased compared with the control（P〈0.01）. The metabolic changes due to nicotine administration involved abnormal glucose, lipid and protein metabolisms, and GD14 was a key time point of the change. During GD11-GD14,nicotine induced the elevation of citrate, glycerol, N-acetyl glycoprotein, valine, leucine, tryptophan, lysine, isoleucine,unsaturated fatty acids, LDL, allantoin（P〈0.05） accompanied with decreased levels in pyruvate, 3-hydroxybutyrate and myoinositol（P〈0.05）. Conclusion NMR-based metabolomic analysis can servered as techniques for detection of metabolic changes of pregnant rats. Pyruvate, 3-hydroxybutyrate, citrate, unsaturated fatty acids, glycerol, valine and leucine may be characteristic metabolites from maternal blood for early warning of abnormal fetal development.

关 键 词：代谢组学 尼古丁 胎儿发育异常 特征代谢物 

分 类 号：R994.6[医药卫生—毒理学]