安神定志灵对ADHD模型鼠前额叶皮质和纹状体多巴胺D1,D2受体表达的影响

Effects of Anshen Dingzhi Ling on Expression of Dopamine Receptor-1 and 2 in Prefrontal Cortex and Striatum in Rats with Attention Deficit Hyperactivity Disorder

摘要:

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-自发性高血压大鼠(spontaneously hypertensive rat,SHR)前额叶皮质、纹状体多巴胺受体D1,D2(DRD1,DRD2)表达的影响,探讨该药治疗ADHD的作用机制。 方法: 30只SHR鼠随机分为5组(模型组、利他林组、安神定志灵高、中、低剂量组),每组6只,Wistar大鼠6只作为正常对照组。安神定志灵高、中、低剂量组分别按生药剂量34.1,17.1,8.5 g ·kg^-1ig;利他林组以2.1 mg ·kg^-1利他林ig;模型组和正常对照组以10 mL ·g^-1生理盐水ig。实验2周后处死大鼠,取脑分别用RT-PCR和Western blot检测各组大鼠前额叶皮质、纹状体内DRD1,DRD2 mRNA和蛋白表达水平。 结果: 模型组与正常对照组比较,DRD1,DRD2 mRNA和蛋白表达水平显著降低(P<0.01);利他林组与模型组比较,DRD1,DRD2 mRNA和蛋白表达水平显著升高(P<0.01);安神定志灵中剂量组与模型组比较,DRD1,DRD2 mRNA和蛋白表达水平显著升高(P<0.01);安神定志灵低剂量组和高剂量组RD1,DRD2 mRNA和蛋白表达水平高于空白模型组,但没有统计学差异。 结论: 安神定志灵可以上调SHR大鼠额叶皮质和纹状体中DRD1,DRD2 mRNA及蛋白的表达水平,说明安神定志灵在调控前额叶-纹状体通路的功能中发挥着重要的作用,而DRD1,DRD2参与了这一调节的过程,最终起到对ADHD的治疗作用。

Abstract:

Objective: To study the influence of Anshen Dingzhi Ling (ADL) on the expression of dopamine receptor-1 (DRD1) and dopamine receptor-2 (DRD2) in prefrontal cortex and striatum of spontaneously hypertensive rat (SHR) model of attention deficit hyperactivity disorder (ADHD), and to investigate the mechanisim of ADL treatment for ADHD. Method: Thirty SHR rats were randomly divided into 5 groups: untreated model group, ritalin group (2.1 mg ·kg^-1 by gavage), 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 and 8.5 g ·kg^-1 respectively). The normal control group includes 5 Wistar rats (given normal saline 10 mL ·kg^-1 by gavage). The rats were killed after 14 days of treatment, then the expression of DRD1, DRD2 mRNA and protein in the prefrontal cortex and striatum of rat brain were detected by RT-PCR and Western blot. Result: Compared with normal group, the levels of DRD1, DRD2 mRNA and protein in model rats reduced significantly (P<0.01); the levels of DRD1, DRD2 mRNA and protein of ritalin group was significantly higher than that in the model group (P<0.01); the levels of DRD1, DRD2 mRNA and protein of the middle dose group was significantly higher than that in the model group (P<0.01);the levels of DRD1, DRD2 mRNA and protein of ADL low dose group and high dose group were higher than that in the model group, but there is no significant difference. Conclusion: ADL can up-regulate the expression of DRD1, DRD2 mRNA and protein in the prefrontal cortex and striatum in SHR, may be related with the influence to the activity of adenylyl cyclase. It shows that ADL plays an important role on regulation to the prefrontal-striatal pathway, and DRD1, DRD2 involved in the adjustment process, the ADL eventually has therapeutic effect for the treatment of ADHD.