静宁颗粒对治疗小儿注意缺陷多动障碍的作用机制研究＊

目的 观察静宁颗粒对注意力缺陷多动障碍（attention deficit hyperactivity disorder,ADHD）模型大鼠行为学及脑内多巴胺能神经的影响,研究静宁颗粒对小儿注意力缺陷多动障碍的治疗作用,探讨静宁颗粒对ADHD模型大鼠的行为学影响的生物学机制,为治疗小儿注意力缺陷多动障碍开发安全长效的中药制剂。方法 采用自发性高血压大鼠（spontaneously hypertensive rats,SHR）作为ADHD的模型大鼠,采用静宁颗粒（20.25 g·kg^-1、10.125 g·kg^-1、5.062 5 g·kg^-1）、盐酸哌甲酯缓释片（6.75 mg·kg^-1）和小儿黄龙颗粒（0.937 5 g·kg^-1）连续给药17 d进行治疗,另设正常对照组,常规饲养。以大鼠自由行动的移动距离、移动速率、敞箱中心区域活动累计时间、身体拉长累计时间等行为学指标,评价药物的药效;采用PCR、Western Blot法测定大鼠大脑前额叶、纹状体部位DRD1、DRD2基因及受体表达水平。结果 与正常对照组比较,模型大鼠移动距离、移动速率、敞箱中心区域累计活动时间、身体拉长累计时间明显升高（P ＜ 0.05,P ＜ 0.01）;与模型组比较,静宁颗粒连续给药17 d后,各剂量可显著降低移动距离、移动速率、敞箱中心区域累计活动时间、身体拉长累计时间（P ＜ 0.05,P ＜ 0.01）,改善ADHD模型大鼠多动及焦虑的症状;并可升高ADHD模型大鼠大脑前额叶皮质、纹状体部位DRD1、DRD2蛋白表达量（P ＜ 0.05,P ＜ 0.01）。结论 静宁颗粒减少ADHD模型大鼠的自主活动,改善ADHD模型大鼠的注意定势转移能力的缺陷,其作用机制可能与升高ADHD模型大鼠大脑前额叶、纹状体部位DRD1、DRD2 mRNA及受体表达水平有关。

Study on the Mechanism of Jingning Granules in the Treatment of Attention Deficit Hyperactivity Disorder in Children

Objective To observe the effects of Jingning Granules on behavior of attention deficit hyperactivity disorder (ADHD) model rats and the brain dopaminergic nerve, to research the treatment effects for children with attention deficit hyperactivity disorder, to explore the biological mechanisms of Jingning Granules s impacts on the behavior of the model rats of ADHD, to develop long-term and safe traditional Chinese medicine (TCM) preparations for the treatment of attention deficit hyperactivity disorder in children. Methods The spontaneously hypertensive rats (SHR) were taken as ADHD rat model. Jingning Granules (20.25 g·kg^-1, 10.125 g·kg^-1, 5.0625 g·kg^-1), Methylphenidate HCl Extended-release Tablets (6.75 mg·kg^-1) and pediatric Huanglong Granules (0.9375 g·kg^-1) administered continuously for 17 days of treatment. The normal control group was set for normal feeding. Index of autonomic activity in rats with moving distance, moving speed, open field center regional activity duration, lengthening of the body total time behavior were used to evaluate drug efficacy. PCR and Western Blot method were used for the determination of rat prefrontal cortex, striatum, DRD2 gene and DRD1 receptor expression level. Results Compared with normal control group, rat model of moving distance, moving speed, open box center area cumulative time, lengthening of the body total time increased significantly (P < 0.05, P < 0.01); compared with the model group, Jingning Granules after 17 days of medication, the dosage can significantly reduce the moving distance, moving speed open the box, center area accumulated time, lengthening of the body total time (P < 0.05, P < 0.01), improve the ADHD rat model of hyperactivity and anxiety symptoms; and raise the level of ADHD in a rat model of prefrontal cortex and striatum of DRD1, DRD2mRNA and the corresponding receptor expression level (P < 0.05, P < 0.01). Conclusion Jingning Granules reduces ADHD model rats of independent activities, improves the model rats of ADHD attention set transfer ability of defect. Its mechanism may be related to increase ADHD model the prefrontal cortex and striatum of rat brain regions DRD1, DRD2mRNA and receptor expression levels.