妊娠中期可卡因对小鼠的发育毒性

目的:探讨可卡因对小鼠妊娠中期的发育毒性,尤其是对脑发育的影响.方法:建立妊娠中期给药的小鼠动物模型,体重相近的妊娠母鼠被分为三组:(1)可卡因注射自由饮食组(COC);(2)盐水注射伴有饮食对照组(SPF),饮食参考体重相近、妊娠时间相同的COC组母鼠;(3)盐水注射自由饮食组(SAL).从妊娠第8天(E8)至第12天(E12)给药,记录母鼠、胎鼠和仔鼠的各项生理指标,并用HPLC分析各组胎鼠纹状体中多巴胺、5-HT含量的变化.结果:尽管COC和 SPF组母鼠与 SAL组母鼠相比摄食量少,体重增加量少,但E17 天取材时,仅COC组胎鼠表现为脑和纹状体重量低;COC组仔鼠生后第 1天(P1)双顶径(BPD)也小于其它两组仔鼠.此外,COC组胎鼠表现出脑/体重比的降低,说明宫内暴露可卡因引起的胎鼠的发育迟缓是一个不平衡过程,脑组织的受累比其它组织严重.神经递质分析和组织学分析表明 COC组胎鼠脑内多巴胺和5-羟色胺的水平增高,肝脏呈现出形态学改变.结论:妊娠中期暴露可卡因可引起胎鼠宫内发育迟缓,尤其是脑发育迟缓.单纯母体营养不良在宫内暴露可卡因引起的后代发育迟缓过程中不能起决定性作用,而可能是药物直接作用的结果.

Developmental toxicity of cocaine exposure in mid-pregnancy mice

AIM: To investigate the toxic effects of mid-pregnancy cocaine exposure on embryo-fetus. METHODS: A trans-placental murine model of cocaine exposure on embryo-fetus mice was established, in which pregnant dams of comparable weight were assigned into three groups: cocaine with food ad lib (COC), saline and pair-fed with COC (SPF), and saline with food ad lib (SAL). From embryonic d 8 (E8) to E17, physiological variables of dams and offspring were recorded and concentrations of dopamine and serotonin in fetal striatum were examined. RESULTS: Compared with SAL dams, COC and SPF dams showed lower weight gain. But only COC fetuses demonstrated low brain weight and low striatum weight on E17, as well as small biparietal diameter (BPD) on postnatal dl (P1). Surprisingly, low brain/body weight ratio was seen in COC offspring, which might reflect disproportionate growth delay in these fetuses. Neurotransmitter and histological analysis revealed high level of dopamine and serotonin in COC fetal striatum, as well as morphological alterations of liver. CONCLUSION: Mid-pregnancy cocaine expo-sure induces fetal growth delay in utero, especially disproportionate brain developmental retardation. Maternal undernutrition does not play a key role in fetal developmental retardation when exposed to cocaine in utero.