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目的:研究安神定志灵对注意缺陷多动障碍(attention deficit hyperactivity disorder,ADHD)动物模型大鼠脑边缘系统多巴胺受体D3(dopamine receptor-3,DRD3)、D4(dopamine receptor-4,DRD4)及D5(dopamine Receptor-5,DRD5)和前额叶皮质DRD4基因表达的影响,探讨该药治疗ADHD可能的作用机制。方法:30只自发性高血压大鼠(spontaneouslyhypertensive rat,SHR)随机分为5组(安神定志灵高、中、低剂量组,利他林组,模型组),6只同龄Wistar大鼠作为正常对照组。安神定志灵高、中、低剂量组分别给予生药剂量34.1,17.1,8.5 g.kg-1,利他林组予2.1 mg.kg-1,模型组和正常对照组予10mL.kg-1生理盐水,各用药组每次均以每天相应剂量的1/2 ig,2次/d,连续给药1月后进行实验处理,迅速分离脑组织,采用RT-PCR检测各组大鼠脑边缘系统DRD3,DRD4及DRD5和前额叶皮质DRD4基因表达水平。参照基因表达谱芯片分析,当目的基因表达≥2,认为该基因表达增高;若≤0.5认为基因表达降低。结果:与正常组比较,模型组大鼠不论是脑边缘系统中DRD3,DRD4和DRD5基因表达还是前额叶皮质中DRD4基因表达均降低。与模型组相比,利他林组脑边缘系统中DRD3,DRD4及DRD5基因的表达和前额叶皮质中DRD4基因的表达均回调;安神定志灵低剂量组回调脑边缘系统中DRD3,DRD4,DRD5的表达和前额叶皮质中DRD4的表达,中剂量组仅发现前额叶皮质中DRD4的表达增加,高剂量组上调脑边缘系统中DRD3的表达的同时显著下调前额叶皮质中DRD4的表达。结论:DRD3,DRD4及DRD5与ADHD的发生存在一定的关联性,不同剂量的安神定志灵在调控中脑-皮质-边缘系统多巴胺通路的功能中发挥不同的作用,提示临床给药剂量需结合临床症状和体征等。
Objective: To investigate the effects of Anshen Dingzhi on dopamine receptor-3 (DRD3), dopamine receptor-4 (DRD4) in the limbic system of attention deficit hyperactivity disorder (ADHD) And D5 (dopamine Receptor-5, DRD5) and prefrontal cortex DRD4 gene expression, explore the drug may be the mechanism of action of ADHD. Methods: Thirty spontaneously hypertensive rats (SHR) were randomly divided into 5 groups (Anshen Dingzhi high, medium and low dose group, Ritalin group, model group) and 6 Wistar rats of the same age as normal Control group. Anshen Dingzhi Ling high, medium and low dose groups were given crude drug dose 34.1,17.1,8.5 g.kg-1, Ritalin group 2.1 mg.kg-1, the model group and the normal control group to 10mL.kg-1 Physiology Saline, and each treatment group was treated with ½ ig, 2 times / d of the corresponding dose every day for 1 month. The brain tissues were quickly isolated and the brain limbic system DRD3, DRD4 and DRD5 and prefrontal cortex DRD4 gene expression levels. According to the gene expression profiling chip analysis, when the target gene expression ≥ 2, that the gene expression increased; ≤ 0.5 if the gene expression is reduced. RESULTS: Compared with the normal group, the expression of DRD3, DRD4 and DRD5 genes in DR model rats and DRD4 gene expression in prefrontal cortex decreased in model group rats. Compared with the model group, the expression of DRD3, DRD4 and DRD5 genes and the expression of DRD4 gene in the prefrontal cortex were all reversed in the limbal system of Liupilin group. The low dose of Anshen Dingzhi Ling regressed DRD3, DRD4 and DRD5 DRD4 expression in the prefrontal cortex was found in the middle-dose group, but DRD4 expression in the prefrontal cortex was significantly decreased in the high dose group. Conclusion: DRD3, DRD4 and DRD5 are associated with the occurrence of ADHD. Different doses of Anshen Dingzhi can play different roles in the regulation of dopamine pathway in the midbrain - cortex - limbic system, suggesting that the dosage should be combined Clinical symptoms and signs and so on.