海洛因暴露对小鼠成瘾和学习记忆相关脑区磷酸化p38 MAPK的蛋白表达的影响

Increase of mouse p38 MAPK phosphorylation in brain regions related to addiction,learning & memory by prenatal heroin exposure

目的：观察海洛因暴露对小鼠成瘾和学习记忆相关脑区的磷酸化p38 MAPK（p-p38）表达的影响,探讨p38 MAPK细胞信号转导通路是否参与了发育早期海洛因暴露引起子代脑发育损伤的分子机制.方法：于胚胎鼠龄9~18d时给孕鼠皮下注射海洛因10mg/（kg·d）,建立子宫内海洛因暴露的小鼠模型.按出生前处理将小鼠分为海洛因和盐水组.蛋白免疫印迹检测两组小鼠前额叶皮层、海马、伏核、杏仁核脑区p-p38的表达改变.结果：与盐水组相比,海洛因组小鼠的p-p38蛋白表达在前额叶皮层、海马、伏核、杏仁核4个脑区均有明显增加（P〈0.05）.结论：海洛因暴露可引起小鼠前额叶皮层、海马、伏核、杏仁核脑区的p-p38 MAPK蛋白表达上调,提示p38 MAPK信号通路可能参与了海洛因损伤小鼠神经发育的分子机制.

AIM： To investigate the expression of phosphorylated-p38（p-p38） MAPK in the brain regions related to addiction, learning and memory in mouse prenatally exposed to heroin. To ascertain whether p38 MAPK signal transduction pathway participates in neurobehavioral teratogenicity induced by maternal heroin abuse. METHODS： Animal model was established by administrating diacetylmorphine （heroin, Purity 98.5%, Product ID No. 171206 - 200614） 10 mg/（kg · d） subcutaneously to pregnant BALB/c mice on Embryonic day（ E ）E9-E18. The offspring were divided into Heroin and Saline groups according to the maternal treatment. The expression of p38 MAPK protein in prefrontal cortex（PFC）, hippocampus （HP）, nucleus aeeumbens （Acb） and amygdala（Amy） was detected by Westem Blot. RESULTS： The p-p38 MAPK protein level was increased dramatically in areas of PFC, HP, Acb and Amy of Heroin group as compared with Saline group （P 〈 0.05 in all cases）. CONCLUSION： E8-E18 prenatal exposure to heroin can induce overexpression of p-p38 in brain regions related to addiction, learning and memory, which indicates that p38 MAPK signal transduction pathway may be involved in neurobehavioral teratogenicity by heroin exposure in uterus.