海洛因暴露对子代小鼠海马凋亡相关基因表达的影响

Effects of prenatal heroin exposure on expression of apoptosis-mediated genes in offspring mouse hippocampus

目的观察子宫内海洛因暴露对小鼠海马caspase-3、Bcl-2和Bax表达的影响,探讨线粒体凋亡通路在海洛因暴露引起子代小鼠神经、行为发育异常中的作用。方法于小鼠胚龄(embryonicday)E9～E18d时,每天给孕鼠皮下注射海洛因10mg/kg,建立子宫内海洛因暴露的小鼠模型。按出生前处理将仔鼠分为空白组(Con)、盐水组(Sal)和海洛因组(Her)。待仔鼠14d时取海马,应用RT-PCR和WesternBlot检测caspase-3、Bcl-2和Bax的表达情况。结果与Con和Sal组相比,Her组仔鼠的caspase-3和Bax的蛋白表达明显增加(P<0.05),而Bcl-2蛋白表达明显下降(P<0.05)。结论海洛因暴露可引起子代小鼠海马caspase-3和Bax表达上调,Bcl-2表达下调,提示线粒体凋亡通路可能参与了海洛因损伤小鼠神经行为发育的分子机制。

Objective To investigate whether prenatal （P） apoptotic mechanism is involved in neurobehavioral defects in hippocampus caused by heroin exposure in uterus. Methods Animal model was established by administering heroin 10 mg/（kg·d） subcutaneously to pregnant BALB/c mice onE9-E18. The offspring were divided into 3 groups according to the maternal treatment： the control （Con）, saline （Sal） and heroin （Her） groups. Hippocampuses of pups were harvested on postnatal day （P） 14, and RT-PCR and Western blot were applied to detect the expressions of caspase-3, Bcl-2 and Bax. Results Alterations in apoptosis-regulating proteins were found, the expressions of caspase-3 and Bax were increased and Bcl-2 expression was decreased at mRNA and protein levpls （P〈 0.05）, indicating an increase in mitochondrial apoptotic pathways in mice prenatally exposed to heroin compared with the controls. Conclusion Heroin exposure may cause the uprogulation of caspase-3 and Bax expressions and downregulation of Bcl-2 expression of offspring mouse hippocampus. We hypothesize that the apoptotic changes may, at least in part, contribute to heroin teratogenicity during development and lead to hippocampus-dependcnt neurobchavioral deficits.