海洛因暴露对小鼠前额叶皮层、海马和伏核caspase 3表达的影响

Effects of heroin exposure on the expression of caspase 3 in prefrontal lobe cortex,hippocampus and nucleus accumbens

目的：观察海洛因暴露对小鼠前额叶皮层（PFC）、海马（HP）和伏核（Acb）脑组织caspase 3表达的影响,探讨发育期海洛因暴露是否干扰了学习记忆和成瘾脑区的细胞凋亡。方法：于胚胎鼠E8-E18 d时,给孕鼠皮下注射海洛因10 mg/（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盐水（Sal）组和海洛因（Her）组,待其14 d脑凋亡高峰期时取PFC、HP和Acb脑区组织,采用RT-PCR和Western blot法检测caspase 3表达变化。结果：与Sal组相比,Her组小鼠的caspase 3 mRNA在PFC、HP和Acb脑区的表达明显增加（P〈0.05）;激活的caspase 3蛋白表达也明显增加（P〈0.05）。结论：海洛因暴露可增加小鼠PFC、HP和Acb脑区caspase 3的表达,提示海洛因可通过诱导相关脑区细胞凋亡增多而发挥其神经毒性作用。

AIM： To investigate the expression of caspase 3 in the brain regions related to addiction, learning and memory in mice prenatally exposed to heroin and to ascertain whether postnatal apoptotic mechanism participates in neurobehavioral teratogenicity induced by maternal heroin abuse. METHODS： A mouse 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） E8-E18. The offspring were divided into heroin （Her） and saline （Sal） groups according to the maternal treatment. The expression of caspase 3 in prefrontal lobe cortex（PFC）, hippocampus（HP） and nucleus accumbens（Acb） was detected by RT-PCR and Western blot on mouse postnatal day （P） 14. RESULTS： The mRNA and protein expression of caspase 3 were significantly increased in the areas of PFC, HP and Acb in Her group compared with Sal group （P 〈 0.05）. CONCLUSION： E8-E18 prenatal exposure to heroin can induce apoptosis through caspase 3 activation in brain regions related to addiction, learning and memory, which indicates that apoptotic mechanism may be involved in neurobehavioral teratogenicity by heroin exposure in uterus.