安神定志灵对自发性高血压大鼠脑中多巴胺受体D3,D4,D5基因表达的影响

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(spontaneously hypertensive 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-,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.

Effects of Anshen Dingzhiling on Expression of Dopamine Receptor-3, Dopamine Receptor-4 and Dopamine Receptor-5 in the Brain of Spontaneously Hypertensive Rats

Objective: To study the influence of Anshen Dingzhiling (ADL) on the expression of dopamine receptor-3(DRD3), dopamine receptor-4(DRD4) and dopamine receptor-5(DRD) in Limbic system and DRD4 in Prefrontal Cortex of spontaneously hypertensive rat(SHR) as an model of attention deficit hyperactive disorder(ADHD), and to investigate the mechanisms of ADL treatment for ADHD. Method: Thirty SHR rats were randomly divided into groups: untreated model group,ritalin group (2.1 mg·kg^-1 by ig),high dose of ADL group,middle dose of ADL group and low dose of ADL group (ig ADL with the crude drug dosage 34.1, 17.1, 8.5 g·kg^-1 respectively). The normal control group includes 6 Wistar rats (given normal saline 10 mL·kg^-1 by ig). The rats were sacrificed after a month of treatment, then the expression of DRD3, DRD4 and DRD5 mRNA in Limbic system and DRD4 mRNA in Prefrontal Cortex of brain were detected by RT-PCR. Result: compared to the normal rats, Regardless of the expression of DRD3, DRD4 and DRD5 in Limbic system or DRD4 in Prefrontal Cortex of brain of model rats were reduced. Compared with the model rats, the expression of DRD3, DRD4, and DRD5 gene in limbic system and that of DRD4 gene in the prefrontal cortex of Ritalin group was called back by Ritalin, the expression of DRD3, DRD4, and DRD5 gene in the limbic system and that of DRD4 gene in prefrontal cortex was called back by the low-dose ADL, only the expression of DRD4 gene in prefrontal cortex was called back by the middle-dose ADL, the high-dose of ADL raised the expression of DRD3 in limbic system significantly meanwhile lowered the expression of in DRD4 frontal cortex. Conclusion: The produce of ADHD had a certain correlation with DRD3, DRD4 and DRD5.The results showed that different dose of ADL played different roles in the regulation of the dopamine pathways of the brain-the cortex-the limbic system, so prompted that the clinical dosage should be considered with symptoms.