To Explore The Efficacy And Mechanism Of Jingning Granules In The Treatment Of ADHD Based On The Action Pathway Of Vitamin D

ObjectiveThe purpose of this study is to further verify the clinical efficacy of Jingning granule in the treatment of children with ADHD of deficiency of both Qi and Yin,to explore the related mechanism of vitamin D and the regulation of negative emotion of ADHD,and to explore other pathways and mechanisms of Jingning granule in the treatment of ADHD model rats,In order to provide more data and theoretical support for Jingning granule in the treatment of this disease.In the aspect of clinical research,we evaluated the clinical efficacy of Jingning granule in the treatment of ADHD by observing that changes of disease efficacy,scale scores and related serum indicators before and after Jingning granule treatment of children with deficiency of both Qi and Yin,and observed the regulation of Jingning ganule on ADHD related negative emotion and the improvement of related indicators of vitamin D pathway.Objective to provide an important clinical basis for the further development and promotion of Jingning granule.In the aspect of experimental research,OFT was used to detect the improvement of behavior and negative emotion of SHR model rats,the expression and content improvement level of some indicators of vitamin D actionpathway in SHR were observed to verify the hypothesis that Jingning granule canact on dopaminergic system by regulating the related factors of the pathway,to provide an important experimental basis for Jingning granule to further develop new drug research and clinical promotionMethodsIn terms of clinical research,25 children with ADHD who met the criteria were enrolled and given Jingning granule orally for 8 weeks.During the treatment period,the general information of the children was recorded,and the scores of SNAP-IV scale,Conners parents questionnaire,cancellation test and TCM Syndrome Scale were recorded at 0,4 and 8weeks of treatment.Serum DA,vitamin D,TH and BDNF were detected at the node of 0 and 8 weeks of treatment.The safety was evaluated at the same time.The clinical efficacy of Jingning granule in the treatment of ADHD and the improvement of the above detection indexes were observed.In terms of experimental study,50 male 4-week-old SHR model rats were randomly divided into 5 groups,Jingning granule high-,medium-,low-dose group,atomoxetine hydrochloride group and model group,with 10 rats in each group.At the same time,10 male 4-week-old Wistar rats were set as normal control group.According to the different groups,they were given Jingning granule high,mediumand low dose suspension,atomoxetine hydrochloride suspension and deionized water by gavage once a day for 6 weeks.After the open field behavior experiment,the expression of TH protein and THmRNA in hypothalamus,DAT protein and DATmRNA in striatum,BDNF protein and BDNFmRNA in hippocampus,GABA content and GAT expression in hippocampus were detected.The serum samples were retained to detect TH and vitamin D content.Objective to observe effect of Jingning granule on the behavior of SHR model rats and improvement of the above indexes.ResultsIn terms of clinical study,compared with the treatment of 0 week,the results of elimination test and SNAP-IV scores were improved at 4 weeks and 8 weeks of treatment.Compared with 4 weeks of treatment,scores of cancellation test and SNAP-IV scale improved significantly at 8 weeks of treatment.Compared with the treatment of 0 week,scores of conduct problems,learning problems,physical and mental disorders,impulsive hyperactivity,anxiety and hyperactivity index of Conners parents scale decreased significantly at 4 weeks and 8 weeks of treatment.Compared with 4weeks of treatment,scores of each factor decreased significantly at 8 weeks of treatment.Compared with the treatment of 0 week,the main syndrome scores of TCM syndrome integral scale were improved at 4 week and 8 weeks of treatment.Compared with 4 weeks of treatment,scores were significantly improved after 8 weeks of treatment.Compared with 0 week treatment,except for complexion and stool,other items of TCM syndrome integral scale were improved at 4 weeks treatment,and significantly improved at 8weeks treatment.Compared with 4 weeks of treatment,8 weeks of treatment in addition to complexion,defecation and other syndromes were significantly improved.After treatment,the total effective rate of disease was 84%,and the total effective rate of TCM syndrome was 84%.Compared with week 0,levels of serum DA,vitamin D and BDNF were significantly increased at week 8,but there was no significant difference in TH.In terms of experimental study,the results of OFT showed that compared with the model group,the total distance,central distance and central time of exercise in the high-,medium-,low-dose Jingning granule groups and the atomoxetine group were significantly reduced,while the total rest time and edge time were significantly increased,especially in the high dose Jingning granule group and the atomoxetine hydrochloride group.Both high-dose Jingning granule group and atomoxetine hydrochloride group could up-regulate the serum TH content of ADHD model rats.Every Jingning granule groups and atomoxetine hydrochloride group could up-regulate the serum vitamin D content of ADHD model rats.The expression levels of TH protein and THmRNA in hypothalamus of ADHD model rats were up-regulated in high-dose Jingning granule group and atomoxetine hydrochloride group.Expression levels of DAT proteinand DATmRNA in striatum of ADHD model rats were down-regulated in Jingning granule high-dose group,middle-dose group and atomoxetine hydrochloride group.The expression levels of BDNF protein,BDNFmRNA in hippocampus of ADHD model rats were up-regulated in high-dose Jingning granule group and atomoxetine hydrochloride group.Each dose of Jingning granule group and atomoxetine hydrochloride group could up-regulate the content of GABA and expression level of GAT in hippocampus of ADHD model rats.ConclusionsIn terms of clinical study,Jingning granule can improve the clinical core symptoms and TCM Syndromes of children with ADHD with deficiency of Qi and Yin,and have some regulatory effect on the related negative emotions.The dopaminergic system of ADHD children is abnormal,Jingning granule can improve its dysregulation,which may play a role in regulating the factors TH and BDNF related to the action pathway of vitamin D.In terms of experimental study,Jingning granule can effectively control the hyperactivity impulse behavior and the negative emotion of ADHD model rats,and its effect is equivalent to that of atomoxetine hydrochloride.The metabolism of dopaminergic system in ADHD model rats is abnormal.Jingning granule can regulate the protein and gene expression of TH,DAT,BDNF and other related factors on the pathway through regulating the action pathway of vitamin D,and improve the disorder of dopamine system in brain,and thus play a therapeutic effect.