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目的 通过建立妊娠中晚期暴露于可卡因的小鼠动物模型 ,探讨可卡因对后代多巴胺能神经系统 (dopaminergicnervoussystem ,DAS)的发育是否具有长时程影响 ,同时探讨这种影响是否具有剂量依赖性和年龄依赖性。方法 称量不同剂量可卡因处理组与对照组的后代仔鼠在青春前期、青春期和成年期的体重和脑重 ;运用高效液相色谱结合电化学检测器 (HPLC EC)的技术检测各组各时期后代仔鼠脑内多巴胺 (dopamime,DA)及其代谢产物 3 ,4 双羟苯乙酸 (3 ,4 di hydroxyphenylaceticacid ,DOPAC)、高香草酸 (4 hydroxy 3 menthoxyphenylaceticacid ,HVA)含量差异 ;通过免疫组织化学结合图像分析方法观察黑质区 (substantianigra,SN)酪胺酸羟化酶 (tyrosinehydroxylase,TH)的分布与含量。 结果 在妊娠期中晚期皮下注射中等剂量可卡因的仔鼠在青春前期和青春期生长发育延迟 ,脑内DA及其代谢产物的含量比对照组明显增高 ,SN区TH相对含量增多 ,这些改变在成年期恢复正常 ;低剂量组的仔鼠各项检测指标在各时期与对照组相比无统计学意义 ;高剂量组的妊娠母鼠流产率为 80 % ,新生仔鼠 1 0d内死亡。结论 妊娠期暴露于可卡因对后代DAS的发育和功能具有长时程影响 ,这种影响具有剂量依赖性和年龄依赖性
OBJECTIVE: To investigate if cocaine has long-term effects on the development of the dopaminergic nervous system (DAS) of the offspring by establishing animal models of mice exposed to cocaine in the second trimester of pregnancy, and to explore whether this effect is dose-dependent and age-dependent Sex. Methods The body weight and brain weight of offspring of adolescent, adolescent and adulthood of cocaine-treated and control groups were measured at different doses. HPLC-ECD was used to detect the changes of body weight and brain weight The contents of dopamine (DA) and its metabolites 3, 4 di-hydroxyphenylacetic acid (DOPAC) and 4-hydroxy-3 menthoxyphenylacetic acid (HVA) in the offspring of offspring were detected by immunohistochemistry The distribution and content of tyrosine hydroxylase (TH) in substantia nigra (SN) were observed by image analysis. Results In the second and third trimester of pregnancy, the middle dose of cocaine infused subcutaneously at a dose-dependent manner showed delayed growth and development in pre-adolescence and adolescence. The levels of DA and its metabolites in brain were significantly higher than those in control group, while the relative content of TH increased in SN area. These changes recovered in adulthood Normal; low dose group of offspring test indicators in each period compared with the control group was not statistically significant; high dose group gestational females miscarriage rate was 80%, newborn pups died within 10 days. Conclusions Exposure to cocaine during pregnancy has a long-term effect on the development and function of the offspring DAS in a dose-dependent and age-dependent manner