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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 changes of metabolites in peripheral blood of pregnant rats exposed to nicotine and to find out the early characteristic metabolites that may reflect the abnormal fetal embryo development. Methods Sixteen Wistar pregnant rats were divided into blank control group and nicotine treatment group. The rats were subcutaneously injected with normal saline and nicotine [2 mg / (kg · d)] respectively at 9-20 d of gestation. The body weight of pregnant rats was observed and analyzed. At the time point (11, 14, 17, 20 d pregnant), the 1H NMR spectrum of plasma was changed. Results After the nicotine treatment, the weight gain of pregnant rats slowed down and the weight of pregnant rats on the 20th day was lower than that of the control group (P <0.01). Pregnant rats plasma glucose, lipid and protein metabolism related to a variety of substances change, pregnancy 14 d is an important time point. From 11 to 14 days pregnant, citric acid, glycerol, N-acetylglucosamine, valine, leucine, tryptophan, lysine, isoleucine, unsaturated fatty acid, LDL cholesterol, (P <0.05), while the concentrations of pyruvate, β-hydroxybutyrate and inositol decreased (P <0.05). Conclusion NMR metabolomics can be used as a means to detect metabolic changes in pregnant rats. Β-hydroxybutyric acid, pyruvic acid, citric acid, unsaturated fatty acids, glycerol, valine and leucine may be used as indicators of fetal development in maternal peripheral blood Abnormal early characteristic metabolites.