出生前尼古丁暴露增加新生大鼠下丘脑orexin A及延髓内orexin 1型受体表达

流行病学调查显示,出生前暴露于烟雾环境是新生儿猝死综合征发生的首位原因,尼古丁是香烟烟雾中最主要的影响胎儿神经系统发育的成分。为了观察出生前尼古丁暴露对新生大鼠下丘脑orexin A(OXA)及延髓内orexin 1型受体(OX1R)表达的影响,本实验将20只雌性成年大鼠随机均分为二组,怀孕后第5 d开始每天分别皮下注射尼古丁6 mg/kg(模型组)或等量的生理盐水(对照组),直至分娩。随机选取模型组和对照组所产的新生大鼠(1～3 d),采用免疫组织化学方法和图像分析技术,观察新生鼠下丘脑内OXA及延髓内OX1R阳性神经元的分布情况。结果显示:两组新生大鼠下丘脑内OXA免疫阳性细胞均有表达,且都主要存在于下丘脑背内侧区与穹窿周围,模型组的新生大鼠OXA免疫阳性细胞的相对光密度(ROD)值高于对照组(P<0.05)。延髓内OX1R免疫阳性细胞在两组内均有广泛分布,主要分布在腹外侧区和舌下神经核。在这两个区域,模型组新生鼠的OX1R免疫阳性细胞的ROD值均高于对照组(P<0.001)。以上结果表明,出生前尼古丁暴露的新生大鼠,下丘脑OXA及延髓内OX1R的表达均上调,提示出生前尼古丁暴露改变了新生大鼠脑内OXA系统递质的释放和突触传递,这意味着脑内orexin系统参与出生前尼古丁暴露导致的各种疾患。

Prenatal nicotine exposure increases the expression of orexin A in the hypothalamus and orexin type 1 receptor in the medulla of neonatal rats

Epidemiological studies suggested that prenatal smoking environment probably is the leading cause of sudden infant death syndrome.As one of the major components in cigarette smoking,nicotine is likely to contribute to the malformation of the nervous system in fetus.To explore the influence on the expression of orexin A(OXA) in the hypothalamus and orexin type 1 receptor(OX1R) in the medulla of neonatal rats after prenatal nicotine exposure,the 20 pregnant rats were divided into 2 groups randomly.Either nicotine(6 mg/kg per day) or normal saline solution(as same volume as nicotine group) was administered into the pregnant rats hypodermically from the fifth day to the end of gestation.The experiment was performed on neonates(1-3 d) who were exposed to nicotine prenatally or not.The expressions of OXA immunopositive neurons in the hypothalamus and OX1R immunopositive neurons in the medulla were observed in neonates of 2 groups by immunohistochemical technology and software of image measure.The present results showed that OXA immunopositive neurons are distributed in the hypothalamus of both groups alike.They were mainly in the dorsomedial hypothalamic nucleus and around fornix of hypothalamus.The relative optical density(ROD) of OXA was higher in the nicotine-exposed neonates than that in the saline neonates(P<0.05).OX1R immunopositive neurons localized extensively within the neonatal medulla of both groups alike.They were mainly in the ventrolateral area and hypoglossal nucleus.The ROD of OX1R was higher in the nicotine-exposed neonates than that in the saline neonates(P<0.001).The above results indicate that prenatal nicotine exposure upregulated the expression of OXA in hypothalamus and OX1R in the medulla of neonates,which alter release and synaptic transmission of orexin system in brain.These results suggest a possible role for the orexin system in mediating disorders caused by prenatal nicotine exposure.