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目的探讨益智宁神颗粒治疗注意缺陷多动障碍的可能作用机制。方法 40只幼年自发性高血压大鼠(SHR)随机分为模型组、益智宁神组、哌甲酯组、托莫西汀组,每组10只;另以10只WKY大鼠为正常组。益智宁神组给予益智宁神颗粒溶液(浓度为3.75 g/ml)按3.75 g/100 g灌胃,哌甲酯组给予盐酸哌甲酯缓释片5 mg/(kg·d)灌胃,托莫西汀组给予盐酸托莫西汀胶囊0.3 mg/(kg·d)灌胃,正常组和模型组给予0.5%生理盐水2 mg/100g体重灌胃,各组均每日1次,持续28天。检测各组大鼠大脑海马多巴胺神经元形态及胶质细胞源性神经营养因子(GDNF)蛋白表达、阳性细胞计数及mRNA表达。结果电镜下益智宁神组海马多巴胺神经元线粒体等结构的损伤程度低于模型组。益智宁神组、托莫西汀组、哌甲酯组大鼠海马GDNF蛋白及mRNA表达高于模型组(P<0.05);托莫西汀组GDNF mRNA高于益智宁神组、哌甲酯组(P<0.05);各组大鼠海马GDNF阳性细胞计数差异无统计学意义(P>0.05)。结论益智宁神颗粒可以减轻SHR幼鼠海马多巴胺神经元损伤程度,提高GDNF蛋白及其mRNA表达,可能是其作用机制之一。
Objective To investigate the possible mechanism of Yizhiningshen granule in the treatment of attention deficit hyperactivity disorder. Methods 40 juvenile spontaneous hypertensive rats (SHR) were randomly divided into model group, Yizhininging group, methylphenidate group and atomoxetine group, with 10 rats in each group. Another 10 WKY rats were normal group. Yizhining Ningshen group was given Yizhining Ningshen granule solution (concentration 3.75 g / ml) by 3.75 g / 100 g gavage, methylphenidate hydrochloride methylphenidate sustained release tablets 5 mg / (kg · d) The mice in the stomach and the atomoxetine group were treated with atomoxetine hydrochloride 0.3 mg / (kg · d) orally. The rats in the normal group and model group were intragastrically given 0.5% saline 2 mg / 100 g body weight once a day For 28 days. The hippocampal formation of hippocampal neurons and the expression of glial cell line-derived neurotrophic factor (GDNF) protein, positive cells and mRNA in hippocampus of rats in each group were detected. Results The damage of mitochondria and other structures of dopamine neurons in hippocampus of YZZ group was lower under electron microscope than that of model group. The expression of GDNF protein and mRNA in the hippocampus of the rats in the Yizhining Ningshen group, the atomoxetine group and the methylphenidate group were higher than those in the untreated group (P <0.05); the GDNF mRNA in the atomoxetine group was higher than that in the Yizhining Ningshen group, (P <0.05). There was no significant difference in the number of GDNF positive cells in the hippocampus of rats in each group (P> 0.05). Conclusion Yizhiningshen granule can alleviate the damage of hippocampal dopaminergic neuron in SHR rats and increase the expression of GDNF protein and its mRNA, which may be one of its mechanisms.