子宫内海洛因暴露对小鼠前额叶皮层海马和伏核P-ERK1／2表达的影响

Effect of prenatal heroin exposure on p-ERK1/2 expression in the prefrontal lobe cortex,hippocampus and nucleus accumbens in mice

目的观察子宫内海洛因暴露对小鼠前额叶皮层（PFC）、海马（HP）和伏核（Acb）脑区磷酸化ERK1／2（P—ERK1／2）表达的影响，探讨ERKMAPK细胞信号转导通路是否参与了发育期海洛因暴露导致小鼠神经行为缺陷的分子机制。方法于胚胎鼠9—18日龄时，每天给孕鼠皮下注射海洛因10mg／kg一次，建立宫内海洛因暴露小鼠模型。按出生前处理将小鼠分为海洛因组（Her）和盐水组（Sal）。RT—PCR和蛋白免疫印迹法检测两组小鼠前PFC，HP和Acb三个脑区组织p-ERK1／2的表达变化。结果与Sal组相比，Her组小鼠的体重无明显变化；p-ERK1／2的mRNA和蛋白表达在三个脑区无明显改变。结论发育期10mg／kg海洛因暴露未损伤小鼠的体格发育，海洛因可能通过ERK1／2MAPK信号通路以外的机制导致神经行为缺陷。

Objective To study the expression of phosphorylated-ERK1/2 （p-ERK1/2）MAPK in the prefrontal lobe cortex （PFC）, hippoeampus （HP） and nucleus accumbens （Acb） in mice exposed to heroin in the uterus, and elucidate whether ERK MAPK signal transduction pathway participates in neurobehavioral teratogenicity induced by matemal heroin abuse. Methods Animal model was established by subcutaneous administration of diacetylmorphine （ 10 mg/kg ·d） to pregnant BALB/c mice on embryonic days 9-18, and their offspring were assigned to heroin and normal saline groups according to the maternal treatment, p-ERK1/2 expression in the PFC, HP and Acb were detected by RT-PCR and Western blot. Results The heroin group had body weights similar to the normal saline group after birth. There were no significant differences in the p-ERK1/2 expression in the PFC, HP and Acb between the two groups. Conclusions Prenatal exposure to 10 mg/kg heroin altered neither the body weight nor the general development in mice. The ERK1/2 MAPK signal pathway might not be involved in the neurobehavioral teratogenieity induced by prenatal heroin exposure.