Clinical Efficacy Evaluation And Its Mechanism Of Anshen Dingzhi Ling In The Treatment Of ADHD With Syndrome Of Exuberant Heart And Liver Fire

Objective To objectively evaluate the clinical efficacy of Anshen Dingzhiling in the treatment of ADHD with syndrome of exuberant heart and liver fire in children.To investigate the effects of saikosaponin-a(SSa)on dopamine content,synthesis,release,clearance it's signaling pathway at the prefrontal cortex in ADHD model of spontaneously hypertensive rats(SHR).Methods Clinical study One hundred and eight children with ADHD were randomly divided into three groups,that is,traditional Chinese medicine(TCM)group,Tomoxetine-treated group,TCM and Tomoxetine-treated group.TCM group was given Anshen Dingzhiling,Tomoxetine-treated group was given Tomoxetine hydrochloride,TCM and Tomoxetine-treated group was given Anshen Dingzhiling combined with Tomoxetine hydrochloride.After 8 weeks,the clinical efficacy and SNAP-IV scale integral,Conners hyperactivity index,TCM syndrome integral improvement rate of the three groups were analyzed.Experimental study Fifty SHR rats were randomly divided into five groups,that is,model group,Ritalin-treated group(2mg/kg),low-dose Ssa treated group(12.5mg/kg),middle-dose SSa treated group(25mg/kg),and high-dose SSa treated group(50mg/kg).In addition,10 Wistar Kyoto rats(WKY)were also served as the normal group.All rats were intragastrically administered with or without SSa twice a day for 4 weeks.After treatment for 4 weeks,protein levels of SNAP-25,Syntaxin-la and TH were measured by western blotting.MAT2,SNAP-25,Syntaxin-la and DAT protein and mRNA levels were detected using qRT-PCR.Immunohistochemistry was used to detect the protein expression of VMAT2 and DAT in prefrontal lobe of rats in each group.In addition,high performance liquid chromatography(HPLC)was used to detect the content of dopamine in the prefrontal cortex of rats.Results Clinical research(1)The total effective rate of the Tomoxetine-treated group was 67.86%,65.71%in TCM group,78.13%in TCM and Tomoxetine-treated group,There was no significant difference between TCM medicine group and Tomoxetine-treated group.TCM and Tomoxetine-treated group(P>0.05),but there was significant difference between Tomoxetine-treated group and TCM and Tomoxetine-treated group(P<0.05).(2)The total effective rate of TCM in Tomoxetine-treated group was 64.29%,77.14%in TCM medicine group,84.38%in TCM and Tomoxetine-treated group.There was no significant difference between Tomoxetine-treated group and TCM group and TCM and Tomoxetine-treated group(P>0.05).There was significant difference between TCM group and TCM and Tomoxetine-treated group(P<0.05).(3)After treatment,SNAP-IV score and Conners hyperactivity index of the three groups were significantly lower than before(P<0.05).There was no significant difference between Tomoxetine-treated group and TCM group in SNAP-IV score and Conners hyperactivity index(P>0.05).There was significant difference between TCM and Tomoxetine-treated group and Tomoxetine-treated group and TCM group(P<0.05).(4)In terms of improving restlessness,multilingualism,impulsiveness,irritability and inattention,there was no significant difference between TCM group and Tomoxetine-treated group(P>0.05).The curative effect of TCM and Tomoxetine-treated group was significantly better than that of TCM group and the Tomoxetine-treated group(P<0.05).(5)In terms of improving dry mouth,short urine and dry stool,the curative effect of TCM and Tomoxetine-treated group and TCM group was significantly better than that of Tomoxetine-treated group(P<0.05).In terms of improving learning difficulties and restless symptoms,the curative effect of TCM and Tomoxetine-treated group was significantly better than that of TCM group(P<0.05).Experimental research Compared with the model group,the expression of TH,VMAT2,SNAP-25,and Syntaxin-la in Ritalin group significantly increased(P<0.05),while DAT expression decreased significantly(P<0.05).Compared with Ritalin-treated group,SSa had the same effect on the above indexes,especially on DAT and Syntaxin-la.Conclusions The clinial part of this study shows that Anshen Dingzhiling has a definite effect in treatment of ADHD with syndrome of exuberant heart and liver fire in children.Its initiation of the effect time is about 2-4 weeks,The initiation of the effect time of topoxetine hydrochloride is abOout 1-2 weeks which is quicker than that of traditional Chinese medicine.However,the effectiveness of TCM on improving the scores of SNAP-IV scale,Conners hyperactivity index and hyperactivity,multilingualism,impulsiveness,irritability and inattention is comparable to that of Tomoxetine hydrochloride.TCM is superior to Tomoxetine hydrochloride in improving dry mouth,short urine and dry stool.The combination of Anshen Dingzhiling and Tomoxetine hydrochloride in the treatment of ADHD with syndrome of exuberant heart and liver fire has the best improvement on SNAP-IV scale score,Conners hyperactivity index and TCM syndrome score.The experimental part of this study shows that SSa could increase the content of dopamine in the prefrontal cortex of ADHD model rats.The mechanism may be related to the the increase of synthesis and release of DA in the prefrontal cortex and the decrease of DA reabsorption.