静宁颗粒对注意缺陷多动障碍模型大鼠下丘脑-垂体-肾上腺轴及多巴胺的影响

Effect of Jingning Granule on Hypothalamus-Pituitary-Adrenal Axis and Dopamine in Attention Deficit Hyperactivity Disorder Rats

目的探讨静宁颗粒对注意缺陷多动障碍(Attention-deficit hyperactivity disorder,ADHD)的作用机制。方法将50只雄性自发性高血压大鼠(SHR)按随机数字表法分为静宁颗粒高、中、低剂量组,盐酸哌甲酯组及模型组,每组10只。同时将10只同龄Wistar大鼠设为正常组。正常组、模型组均按1 mg/100 g给予生理盐水;盐酸哌甲酯组按1 mg/100 g给予盐酸哌甲酯混悬液;静宁颗粒组按1 mg/100 g给予不同浓度的颗粒混悬液,具体浓度静宁颗粒高、中、低剂量组分别23.14 g/kg、11.57 g/kg、5.79 g/kg,1次/d,连续6周。运用高效液相法检测纹状体多巴胺(Dopamine,DA)及其代谢产物含量[二羟基苯乙酸(DOPAC)]。采用酶联免疫吸附测定法(Enzyme linked immunosorbent assay,ELISA)检测血清中促肾上腺皮质激素(Adrenocorticotropic hormone,ACTH)、皮质醇(Cortisol,COR)的表达量。结果与正常组比较,模型组大鼠纹状体DA及DOPAC含量下降,其中DA含量下降,差异有统计学意义(P<0.05);经药物干预后,与模型组比较,盐酸哌甲酯组、静宁颗粒高剂量组DA及DOPAC含量明显上升(P<0.05)。与正常组比较,模型组ACTH、COR含量均下降(P<0.05,P<0.01)。与模型组比较,静宁颗粒高、中、低剂量组,盐酸哌甲酯组ACTH含量均有不同程度提升,除静宁颗粒低剂量组外,其余组别与模型组比较,差异均有统计学意义(P<0.05,P<0.01),静宁颗粒高、中、低剂量组,盐酸哌甲酯组组间比较,差异无统计学意义(P>0.05);与模型组比较,除静宁颗粒中剂量组外,各组COR含量均有明显提升(P<0.01)。结论静宁颗粒可能通过介导SHR大鼠HPA轴功能以调节纹状体DA水平,达到控制注意缺陷多动障碍临床症状的目的。

Objective To investigate the mechanism of Jingning Granule on attention deficit hyperactivity disorder(ADHD).Methods 50 male Spontaneously Hypertensive Rat(SHR)rats were divided into Jingning granule high-,medium-,and low-dose group,methylphenidate hydrochloride group and model group according to the random numbers table method,with 10 rats in each group.At the same time,10 Wistar rats of the same age were set as the normal control group.The normal group and the model group were given normal saline at 1 mg/100 g;the methylphenidate hydrochloride group was given methylphenidate hydrochloride suspension at 1 mg/100 g;the Jingning granule group was given different concentrations of 1 mg/100 g For the granule suspension,the specific concentration of Jingning granule high,medium and low dose groups were 23.14 g/kg,11.57 g/kg,5.79 g/kg,1 time/d,for 6 consecutive weeks.The content of striatal dopamine(DA)and its metabolites[dihydroxyphenylacetic acid(DOPAC)]was detected by HPLC.Enzyme linked immunosorbent assay(ELISA)was used to detect the expression of adrenocorticotropic hormone(ACTH)and cortisol(COR)in serum.Results Compared with the normal group,the content of DA and DOPAC in the striatum of the model group decreased,and the content of DA decreased,and the difference was statistically significant(P<0.05);after drug intervention,compared with the model group,methylphenidate hydrochloride The DA content in the Jingning granule high-dose group andthe Jingning granule group increased significantly(P<0.05).Compared with the normal group,the content of ACTH and COR in the model group decreased(P<0.05,P<0.01).Compared with the model group,the ACTH content of the Jingning granule high,medium,and low dose groups,and the methylphenidate hydrochloride group all increased to varying degrees.Except for the Jingning granule low dose group,the other groups had statistical differences compared with the model group.Significance(P<0.05,P<0.01).There was no statistically significant difference between the Jingning granule high,medium and low dose groups and the methylphenidate hydrochloride group(P>0.05);compared with the model group,Chujingning Except for the granule medium-dose group,the COR content of each group was significantly increased(P<0.01).Conclusion Jingning Granule may improve the clinical symptoms of ADHD by modulating the function of HPA axis in SHR rats,so as to regulate the DA level of striatum.