Effects Of Jingning Granules On Attention Deficit Hyperactivity Disorder Children With Qi-Yin Deficiency Syndrome And SHR Monoamine Mechanism

Objective:1.To observe JingNing granule in the treatment of attention deficit hyperactivity disorder qi and Yin deficiency type of children,the change of rating scale and follow-up results,and comparison with the static ling oral liquid group,evaluate the clinical curative effect of treating ADHD JingNing particles,as well as provide JingNing particles long curative effect in treatment of the disease,for his own further significant new drug research.2.Using Morris water maze test animal models with ADHD-young spontaneously hypertensive rats(SHR)learning and memory ability,evaluation JingNing granule on SHR rats,the effect of cognitive function and observe JingNing particles in the striatum of SHR rats single amine neurotransmitter DA,NE,5-HT,DOPAC,5-HIAA and DATmRNA expression in the prefrontal cortex and striatum,explore the mechanism of action of JingNing granule in the treatment of ADHD,for his own clinical experimental support and basis for the development of new drugs.Methods:Clinical research,in September 2014 to January 2017 and conform to the American psychiatric association's diagnostic and statistical manual of mental disorders in 2013 fifth edition(DSM-V)diagnostic criteria for ADHD and standard of syndromes of TCM of ADHD children with 60 cases according to random number table were randomly divided into JingNing particle group 30 cases and static ling oral liquid in the control group 30 cases,the treatment group with Chinese medicine JingNing particles,the control group taking jing ling oral liquid treatment,a course of 12 weeks,observe efficiently,attention deficit hyperactivity disorder scale before and after the treatment(SNAP-IV),TCM syndrome score,behavior rating scale,Conners parents questionnaire scores,hyperactivity of index,the cancellation test to improve the situation as well as the blood,urine,stool routine checks;Liver(ALT),kidney(BUN,Cr)function;Ecg examination.Record the adverse events.Treatment is used for the effective cases in February after follow-up of attention deficit hyperactivity disorder scale,effective cases of long-term curative effectAnimal experiment research,4 weeks old SHR rats 60,adaptive 3d after feeding,SHR rats were randomly divided into 6 groups,JingNing party high,medium and low dose groups ritalin,hydrochloric acid,hydrochloric acid using 3-phenyipropanol paxil group,model group,10 in each group.Will age Wistar rats 10 set as normal control group.Group to fill the stomach,JingNing granules dosage of high dose of 23.14 g/kg respectively,low dose of 11.57 g/kg,5.785 g/kg dose;Ritalin hydrochloride dosage of 3.86 mg/kg;Hydrochloric acid dosage of mo paxil group was 5.36 mg/kg;Model group and normal control group to the amount of distilled water to fill the stomach,groups of lavage 1 times a day.six weeks of continuous treatment After 6 weeks to medicine every day for a Morris water maze experiment testing each cognitive function in rats;Behavioral observation after the execution,high performance liquid-electrochemical detection(HPLC-ECD)in the rat striatum single amine neurotransmitter DA,NE,5-HT,DOPAC,the expression of 5-HIAA,using Real Time polymerase chain reaction(PCR)detection in the prefrontal cortex and striatum of rats DATmRNA transcription level changes.Results:After three months of treatment,the treatment group 28 cases,5 cases were markedly improved(17.9%),effective 19 cases(67.9%),4 cases were ineffective(14.2%),the clinical total effective rate was 85.71%;In the control group,26 cases,4 cases were markedly improved(15.4%),effective,17 cases(65.4%),invalid in 5 cases(19.2%),the clinical total effective rate 80.77%;Compared two groups of clinical curative effect,have no significant difference(P>0.05).In terms of the improvement of TCM syndrome,the main certificate,certificate of traditional Chinese medicine treatment group before and after treatment had obvious statistical difference(P<0.05),improve the effect is obvious;Control master of traditional Chinese medicine syndrome(hyperactivity restless,concentration),time card(little sleep much dream,hand,foot and heart heat,dry mouth and spontaneous sweating,night sweats,tongue veins)before and after treatment are also statistically significant(P<0.05);The two groups after therapy of traditional Chinese medicine certificate was not China difference was statistically significant(P<0.05).The control group after treatment of traditional Chinese medicine master card(hyperactivity restless,concentration),time card(little sleep much dream,hand,foot and heart heat,spontaneous sweating,night sweats,dry mouth and tongue veins)was also improved,the difference is statistically significant(P<0.05).The two groups after treatment with TCM syndrome was not improved,the treatment group is better than that of control group,the difference was statistically significant(P<0.05).Treatment group after treatment with scale score was significantly decreased,the difference is statistically significant(P<0.05);Control group after treatment,scale scores before the treatment has no obvious improvement,there was no statistically significant difference(P>0.05);Scale scores improved compared to the two groups after treatment in treatment group than the control group after treatment after treatment ADHD scale scores reduced obviously,the treatment group is better than that of control group,the difference statistically significant(P<0.05).The treatment group after treatment with hyperactivity index was significantly decreased,the difference was statistically significant(P<0.05);The control group after treatment with hyperactivity index was also have significantly reduced,the difference was statistically significant(P<0.05);Two groups of children with hyperactivity index improved after treatment there was no statistical significance(P>0.05).Treatment group after treatment with leakage row number of words to improve significantly lower than before treatment,there are significant difference(P<0.01),the control group after treatment with leakage row number of words to improve before the treatment also significantly reduced,with significant difference(P<0.01);Two groups of cancellation score before and after treatment were statistically significant(P<0.05);The two groups after treatment with leakage row number of words there are statistically differences(P<0.01),the treatment group is better than the control group;After treatment with differentiating words to improve the comparison of differences had no statistical significance(P>0.05).The two groups after treatment of soft neurological signs improved,significantly lower positive rate,negative rate increased significantly.Two groups of children during taking JingNing particles and static ling oral liquid,blood,urine,liver(ALT),kidney(BUN,Cr)function,electrocardiogram(ecg)and other safety indexes in the normal reference value range,no serious adverse reactions happen.Each group of rats,the effects of navigation:2,3 days,model group extended escape latency period compared with control group rats(P<0.05),compared with the model group mice,focused on rat escape latent period 2 days of group was obviously shortened(P<0.05),3 days compared with model group,the escape latency time JingNing high dose group,focus groups,JingNing low dose group were shortened(P<0.05).4,5 days,the model group rats compared with control group rats were significantly prolonged(P<0.01),JingNing high dose group,low dose group,JingNing in JingNing dose group compared with model group,has shortened(P<0.05),the fifth day JingNing rat escape latent period and low dose group compared to choose the sida group time shorten(P<0.05).Compared with normal group,choose the sida group rat escape latent period prolonged(P<0.05).Groups of rats,the effects of space exploration;2 day,model group compared with control group,focus groups,prolong swimming distance(P<0.05).3 days,JingNing low dose group,the focus of group and normal group compared with model group,rats swimming distance decreased(P<0.05).4,5 days,model group compared with control group and the intervention group,the swimming distance are extended(P<0.05).JingNing particles each dose group compared to choose the sida group and normal group were no obvious difference(P>0.05).Each rat spatial learning and memory ability to maintain the effect:Morris water maze from experimental rats of target quadrant residence time and the number of cross platform:rats compared with control group,model group rats target quadrant residence time shortened(P<0.05),and compared with model group,with the exception of JingNing high dose group,the intervention group,all target time extension(P<0.05).Choose the sida group and JingNing dose group,the JingNing low-dose group and model group compared with the target residence time are extended(P<0.05).Model group rats crossing platform within 60 s number compared with the control group rats reduced(P<0.05),JingNing particles,low set,choose the sida group compared with model group through the increase(P<0.05).JingNing particles each dose group compared with normal group and choose the sida group through the platform number has no obvious difference(P>0.05).Striatum and prefrontal dopamine transporter(DAT)mRNA expression level comparison:For in the prefrontal cortex of rats DAT mRNA expression level,the differences between the groups.Choose the sida group compared with normal group,DAT mRNA expression in rat striatum 2 or more times,that the gene expression increased;Compared with model group,low dose group,the focus of group DAT JingNing particles mRNA expression 1/2 times or less,that the gene expression.HPLC-ECD neurotransmitter comparison results:compared with model group,normal control group and JingNing striatum in low dose group rats had NE,DA and 5-HT content increased obviously,choose the sida group DOPAC,5-HT content increased;Compared with the normal control group,JingNing particles in high dose group of NE,DA content decreased significantly;Compared to choose the sida group,JingNing in 5-HIAA lower dose group.Conclusion:JingNing particles can improve the Qi and Yin deficiency syndrome clinical core of children with ADHD symptoms(hyperactivity restless,inattention,low learning efficiency)and secondary symptoms(little sleep much dream,hand,foot and heart heat,spontaneous sweating,night sweats,dry mouth and tongue veins),improve the children with ADHD scale scores,improve the concentration of children with ADHD,the clinical treatment of total curative effect and static ling oral liquid,effectively has the function of kidney so as to achieve the effect of ning god puzzle.Qi and Yin,but JingNing particles on ADHD qi and Yin deficiency syndrome has obvious curative effect,clinical can have the effect of qi and nourishing Yin.And JingNing granule on ADHD Qi and Yin deficiency type the patient's overall intervention is safe,no obvious adverse reactions.JingNing particles can affect the SHR rats escape latency and swimming distance,and can influence from rats in the target quadrant after his residence time and the number of crossing platform,so can make SHR rats spatial learning and memory ability is improved.From the experimental results,compared with the positive clinical first-line drug selection sida,JingNing particles can improve the ability to remember a little time.JingNing particles can improve the rat striatum,DA,NE,5-HT content in lower DAT in the striatum and prefrontal mRNA expression level,shows JingNing granule group and the focus of one,to be able to downgrade SHR rats frontal-striatal loop DAT mRNA expression level,reduce the heavy intake of presynaptic neurons to DA,increase the synaptic cleft of DA concentration,improving the function of central nerve signal transduction of DA,and thus play a role on the treatment of ADHD.