孕期尼古丁暴露对子代大鼠脑组织单胺类神经递质水平的影响

Effects of Gestational Exposure to Nicotine on Levels of Monoamine Neurotransmitters in Brain Tissues of Rat Offspring

[目的]探讨孕期尼古丁暴露对子代大鼠脑组织单胺类神经递质水平的影响。[方法]24只SD受孕大鼠,随机分为4组,即对照组和1.0、2.0、4.0 mg/kg染毒组,每组6只。孕7天起,对照组孕鼠皮下注射生理盐水1 m L,染毒组孕鼠皮下注射尼古丁生理盐水溶液1 m L(各染毒组按1.0、2.0、4.0 mg/kg计算尼古丁量),1次/d,直至分娩。测定5周龄子鼠体重、脑重,计算脑脏器系数;测定5周龄子鼠大脑皮质和海马中去甲肾上腺素(NE)、多巴胺(DA)和五羟色胺(5-HT)的质量分数(后简称"含量")。[结果]4.0 mg/kg染毒组子鼠脑重和脑脏器系数低于另3组(P<0.05)。3个染毒组子鼠大脑皮层NE、DA和5-HT含量均低于对照组(P<0.05);4.0 mg/kg染毒组子鼠NE含量低于另2个染毒组(P<0.05),2.0、4.0 mg/kg染毒组子鼠DA含量低于1.0 mg/kg染毒组(P<0.05),4.0 mg/kg染毒组子鼠5-HT含量低于1.0 mg/kg染毒组(P<0.05)。3个染毒组子鼠海马NE和DA含量均低于对照组(P<0.05);海马DA含量与染毒剂量间呈剂量-效应关系(P<0.05),4.0 mg/kg染毒组子鼠海马5-HT含量低于对照组(P<0.05)。[结论]孕期尼古丁暴露影响子代大脑皮层和海马单胺类神经递质含量,可能参与其导致的神经发育毒性过程。

［Objective］ To evaluate the effects of gestational exposure to nicotine on the levels of monoamine neurotransmitters in various brain regions of rat offspring. ［Methods］ Twenty-four pregnant SD rats were randomly divided into four groups and treated with nicotine saline at dose of 0.0, 1.0, 2.0, and 4.0 mg/kg daily through subcutaneous injection starting from the seventh gestational day until delivery. At the age of 5 weeks, the body and brain weights of offspring were measured, brain organ coefficient was calculated, and the levels of norepinephrine （NE）, dopamine （DA）, and 5-hydroxytryptamine （5-HT） in cerebral cortex and hippocampus of offspring were detected. ［Results］ The brain weight and brain organ coefficient of the 4.0 mg/kg nicotine treatment group were significantly lower than those of the other three groups （P 〈 0.05）. In offspring cerebral cortex, the levels of NE, DA, and 5-HT of the three nicotine exposed groups were significantly lower than those of the control group （P 〈 0.05）; the level of NE of the 4.0 mg/kg nicotine treatment group was significantly lower than those of the other two nicotine exposed groups （P 〈0.05）; the levels of DA of the 2.0 mg/kg and 4.0 mg/kg nicotine exposed groups were significantly lower than that of the 1.0 mg/kg nicotine exposed group （P 〈 0.05）; the level of 5-HT of the 4.0 mg/kg nicotine exposed group was significantly lower than that of the 1.0 mg/kg nicotine exposed group （P 〈 0.05）. In offspring hippocampus, the levels of NE and DA of the three nicotine exposed groups were significantly lower than those of the control group （P 〈 0.05）; a dose-effect relationship was found between the DA level and the dose of nicotine treatment （P 〈 0.05）; the level of 5-HT in the 4.0 mg/kg nicotine exposed group was significantly lower than those of the control group （P 〈 0.05）. ［Conclusion］ Gestational exposure to nicotine could influence the levels of monoamine neurotransmitters in the cerebral cortex and hippocampus of rat offspring, which might participate the neurodevelopmental toxicity induced by nicotine.