The Study Of Jingning Granule On Clinical Efficacy And SHR Dopamine System In Children With Attention Deficit Hyperactivity Disorder

Attention Deficit Hyperactivity Disorder,also known as children’s childhood common neural mental Disorder,its core symptoms including inattention,excessive activity and emotional impulse.According to its typical clinical manifestations,it can be divided into three types:impulsive hyperactivity,attention deficit and mixed type.Because of its unique typical symptoms,the disease influences children’s education,interpersonal relationship,as well as negative impact on social life and other aspects,which brings heavy burden to their families,and even the whole society.Therefore,active and effective treatment is extremely important.ADHD is difficult to treat,for the long course and easy to repeat.Professor is devoted to the basic and clinical research of the disease,and summarizes that the pathogenesis is the imbalance between Yin and Yang and the five organs,combined with the symptoms of"moves restlessly",Professor Wang thinks that the emergence of the disease mainly results from insufficient Yin,that leads to yang excessive,based on this,Professor Wang made Jingning Formula in treating with ADHD and is effective for the type of deficiency of both qi and yin.Some progress has been made on the basis of preliminary experiment and clinical research.In this paper,we discuss the mechanism of Jingning Formula in the treatment of ADHD,and explore the target of improving the symptoms of children with ADHD.This study includes two parts:clinical and experimental.Experiment part is divided into two parts:(1)For the DA recepetors(D1,D2 receptors)of SHR rats.Research includes:ELAISA method was used in detecting the dopamine(DA)content in the striatum and prefrontal cortex of rats;and Western blot method to detect the Dl,D2 receptor expression levels in the striatum.(2)the study of the AC/cAMP/PKA signaling pathway in the DA signal pathway of SHR rats included:ELAISA method was used to detect the content of cAMP in the striatum of rats,and Western blot method was used to detect the protein level of PKA in the striatum.Clinical observation:the clinical efficacy and safety evaluation of Jingning Formula in the treatment of attention defncit hyperactivity disorder of qi and Yin deficiency type.Objective:1.By comparing Jingning Formula in the treatment of attention deficit hyperactivity disorder of qi and Yin deficiency type with the SNAP-IV scale points before and after the change,and compared with Atomoxetine,evaluate the clinical curative effect of JingNing Formula in treating with ADHD.2.By observing JingNing Formula in the treatment of attention deficit hyperactivity disorder of qi and Yin deficiency type with children Conners scale before and after and compared with Atomoxetine,evaluate the effect of JingNing Formula in the treatment of ADHD with different behavioral problems.Method:According to different therapeutic regimen,30 children of attention deficit hyperactivity disorder(qi and Yin deficiency type)from Dongzhimen Hospital are belong to Chinese Medicines group,30 children from Peking University Sixth Hospital are set to the western medicine control group.Treatment group are taking Chinese medicine of JingNing Formula,the control group using Atomoxetine,after 12 weeks,contrast before and after treatment in children with attention deficit hyperactivity disorder scale(SNAP-IV)and Conners parents questionnaire scores.The blood routine,urine routine,liver function,renal function were performed before and after the drug administration.The adverse reactions occurred during the treatment were followed up.Results:For SNAP-Ⅳ,compared with the clinical treatment effect of the two groups,the comparison between the Chinese medicine group and the western medicine group showed statistically significant difference between the two groups.There was no significant difference between Chinese medicine group and western medicine group.In the Conners scale,the traditional Chinese medicine group indicated that there was a statistical significance in behavioral problems,learning problems and hyperactivity problems.The differences between the western medicine group in improving behavioral problems,learning problems,physical problems and hyperactivity were statistically significant.The comparison between the two groups was not statistically significant.There is no serious adverse reactions happen in both two groups of children.Conclusion:JingNing formula can effectively improve the clinical core of children with ADHD symptoms.It improves children with SNAP-IV scale scores,and parents conners scale,the clinical curative effect was similar to Atomoxetine,and no adverse reactions happens.Experiment 1:the regulation effect of jingning formula on DA content and D1 and D2 receptor family in ADHD rats.Objective:To observe the learning and memory ability of spontaneous hypertensive rats(SHR)in the step-down test and evaluate the feasibility of SHR rats as ADHD model rats.The effects of jingning formula on the cognitive function of SHR rats were evaluated and the effects of jingning formula on the content of dopamine and its receptor in the striatum of SHR rats were observed.Method:50 male SHR rats were raised in barrier environment,the adaptive feed three days later,rats were weighing,serial number,and randomly divided into 5 groups according to random number table method.The groups including model group,JingNing high,medium and low dose group,and atomoxetine group,10 in each group.Ten Wistar rats of the same age were set as normal control group.Chinese traditional medicine group according to the high,medixum and low dose made of JingNing formula with distilled water,dosage of high dose of 23.14 g/kg,medium dose of 11.57 g/kg,low dose of 5.785 g/kg,the western medicine group using capsule with dosage of 5.36 mg/kg.The model group and the normal group were given the same amount of distilled water.Each group was treated one time a day for 6 weeks,after 6th week,the experiment was carried out.The content of dopamine in the striatum was detected by ELAISA method.The expression levels of D1 and D2 receptors were detected by Western blot method.Results:Compared with the blank control group,the incubation period of the model group was significantly shorter than that of the control group(P<0.01).The results showed no statistical significance(P>0.05).The avoidance latency of each drug group was significantly shorter than that in the normal group,and the results were statistically significant(P<0.05).The incubation period of western medicine group was slightly shorter than that of traditional Chinese medicine group,but the difference was not obvious(P>0.05).The number of errors in the model group was higher than that in the normal group,and the difference was statistically significant(P<0.01).The number of errors was significantly decreased in each drug group and the model group,and the differences between the other groups in the treatment group except the high-dose group were statistically significant(P<0.05).The number of errors was slightly more than that in the model group.Except for the high-dose group,the difference between the other groups and the blank group was not statistically significant(P>0.05).The number of errors between Chinese traditional Chinese medicine and western medicine group was significantly different(P>0.05).In neurotransmitter detection,the amount of DA in the model group was significantly lower than that in the blank group,and the difference was statistically significant(P<0.01).The amount of DA in each drug group was higher than that in the model group,but the difference was not statistically significant(P>0.05).The amount of DA in each drug group was lower than that in the blank group,and the difference between the other groups and the blank group was statistically significant(P<0.01).The amount of DA in each group was lower than that in the western medicine group,but the difference was not statistically significant(P>0.05).In the model group,the DA content of the frontal lobe was significantly lower than that in the blank group,and the difference was statistically significant(P<0.01).The content of DA in each drug group was higher than that in the model group,and the difference between the other groups and the model group was statistically significant(P<0.05).The content of DA in each drug group was lower than that in the blank group,but there was no statistically significant difference between the other groups and the blank group except for the high-dose group of traditional Chinese medicine(P>0.05).There was no significant difference between the DA content and the western medicine group(P>0.05).The results of the receptor ratio indicated that the model group D2/D1 was less than the blank group,and the difference was statistically significant(P<0.01).The D1/D2 dosage group were slightly greater than the model group,the western medicine group compared with model group difference was statistically significant(P<0.05),the others each dosage group there was no statistically significant difference compared with model group(P>0.05);Each/D1,D2 dosage group were less than a blank,in one of the traditional Chinese medicine dose group had signifieant differenee compared with the blank group statistics meaning(P<0.01),the rest of the group and the blank group comparison difference had no statistical significance(P>0.05);In the western medicine group,D2/D1 was slightly higher than that in the Chinese traditional Chinese medicine group,and the difference was not statistically significant(P>0.05).Conclusion:1.SHR rat is an ideal animal model of ADHD,and there is evidence from behavioral and pathological evidence that it is highly consistent with the ADHD model.2.Jingning formula can effectively enhance the learning and memory ability of SHR rats.3.The amount of DA in the mouse striatum and the prefrontal lobe of the ADHD model decreased,and the D1 and D2 receptors were not sufficient,and the jingning formula could effectively improve DA and its receptor content.4.The hyperactive D1 receptor in the ADHD model may be the most important cause of ADHD.Jingning formula may be effective in treating ADHD by alleviating this hyperactive tendency.Experiment 2:The effect of Jingning formula on AC/cAMP/PKA signaling pathway in ADHD rats.Objective:To observe the intervention effect of jingning formula on cAMP and PKA in rats with ADHD.Method:same as before.Results:the cAMP in the model group was significantly higher than that in the normal control group,and the difference was statistically significant(P<0.01).The cAMP content of the western medicine group was significantly lower than that in the model group,and the difference was statistically significant(P<0.01).The cAMP content of the high-dose group was significantly lower than that in the model group,and the difference was statistically significant(P<0.05).In the low-dose group and the dose group in traditional Chinese medicine,the cAMP content was lower than the model group,but the difference was not significant(P>0.05).The cAMP content of striatum in each drug group was lower than that in the control group,and the difference between the low and medium dose group was significant,and the difference was statistically significant(P<0.01).There was no significant difference between the western medicine group and the high-dose group and the blank group,and the difference was not statistically significant(P>0.05).After administration,the cAMP content of the western medicine group was closest to that of the control group.cAMP of middle and low group was significantly higher than that in western medicine group,and the difference was statistically significant(P<0.05).The cAMP content of high-dose group was higher than that in western medicine group,but the difference was not obvious,and there was no statistical significance(P>0.05).PKA results in the striatum were significantly higher than those in the control group(P<0.01).Compared with the model group,the striatum PKA of each drug group was lower than the model group,but the difference was not statistically significant(P>0.05).The content of PKA in each drug group was higher than that in the blank control group,but the difference was not obvious,and there was no statistical significance(P>0.05).There was no significant difference between each drug group,and there was no statistically significant difference between the groups(P>0.05).Conclusion:1.ADHD model rat showed D1 receptor function in hyperfunction and AC/cAMP/PKA signaling pathways in the striatum are thrilled,with the target protein PKA generate too much,this may be the main and the most direct cause of ADHD children with hyperactivity and impulsiveness.2.JingNing formula may reduce the target protein synthesis of PKA through ease the growing trend of hyperthyroidism,and effectively reduce the AC/cAMP/PKA signaling pathways of excitability,so as to achieve the purpose of the treatment of ADHD.