Regulatory Mechanism Of Anshen Dingzhi Ling On D1R/D2R Signaling Pathway And Receptor Desensitization/Resensitization In ADHD Model Rats

Part One Experimental animal research progress on ADHD treated by Chinese medicine and standardization discussionObjective:By researching related articles,we want to summarize on ADHD treatment by Chinese medicine.Combine with the latest research abroad,we do analysis and discussion about the questions in experiment,then give the relatively reasonable solution.It is hoped that to normalize ADHD treatment by Chinese medicine in this way,in order to get the social identity.Methods:From Chinese,searching thesis in CNKI,VIP and Wanfang Database.Key words are"????????" or "????" or "?????" or "???????","?? " or "?? " or "?? " or "??","?? ".From English,searching ones in Pubmed Database.Key words are "ADHD" or "hyperactivity" or "attention deficit" or "minimal brain dysfunction","Chinese medicine","rats" or "mouse" or "experiment".Result:This research contains 44 articles about ADHD treatment by Chinese medicine,and 4 doctor thesis and 6 master in addition.No relative ones in foreign magazines.Although these articles show the experimental animal research progress on ADHD treated by Chinese medicine,we found some disadvantage.Conclusion:The articles about ADHD treated by Chinese medicine have some problems,but it set the foundation of treatment mechanism.From the content,the animal model,test way,test content and test instrument is close to international ones.We need to do experiment design and standardize operation,and improve the approval from international medicine.Part TWO Regulatory mechanism of Anshen Dingzhi Ling on D1R/D2R signaling pathway and receptor desensitization/resensitization in ADHDObjective:To investigate the effects of Anshen Dingzhi Ling(ADL)on regulatory mechanism of D1R/D2R signaling pathway and receptor desensitization/resensitization in spontaneously hypertensive rats' striatum and prefrontal cortex.Methods:Ten Wistar Kyoto rats constitute normal control group.50 SHR rats were rand omly divided into 5 groups including model group,methylphenidate(MPH)group(2 m g·kg-1 by gavage),and high,middle,low dose of ADL groups(ig ADL with the crud e drug dosage 6.7,13.4,26.7 g·kg-1 respectively).Real-time PCR,Western blot and im munohistochemistry were used to test the Gas,Golf,Gai,AC,cAMP,CDK5,p35,DARPP32,PP 1,CREB,Akt,GSK-3p,?-catenin,PKA,GRK-6,?-arrestin2,NCS-1,PP2A and PSD-95 in SHR ra ts' striatum and prefrontal cortex.Results:(1)ADL can improve the protein and mRNA expression of Gas?Golf and Gi in SHR rats' striatum and prefrontal cortex.(2)ADL can improve the content of AC and cAMP in SHR rats' striatum and prefrontal cortex.(3)ADL can improve the expression of CDK5,p35 and CREB,decrease the expression of PP1 and DARPP32.(4)ADL can improve the expression of PP2A,Akt and ?-catenin,decrease the expression of GSK-3?.(5)ADL can improve the expression of ?-arrestin2,NCS-1,PSD-95,PP2A,PKA and reduce the GRK-6 expression.(6)Saikosaponin a(SSa)can reduce hyperactivity and improved the spatial learning memory deficit in SHR rats.Also,an increased DA concentration in the prefrontal cortex and striatum were observed after treating with the SSa in SHR rats.SSa also can reduce the DAT expression and increase BDNF expression.Conclusion:(1)ADL can influence downstream of DA signal pathway by up-regulate the expression of Gas,Gaolf,Gai,AC,cAMP and PKA.ADL also can down-regulate the expression of PP1 and DARPP32 by up-regulating the expression of CDK5 and p35,to increase the CREB expression in the nucleus in the end.(2)ADL can influence the DA signal pathway not belongs to GRCP by down-regulate GSK-3?,up-regulate PP2A,Akt and ?-catenin.More signal information can be transduced from outside to intracellular in this way to get the effect of treatment.(3)ADL can up-regulate the expression of ?-arrestin2,NCS-1,PSD-95,PP2A and PKA,down-regulate GRK-6 to reduce the desensitization of DA receptor.(4)SSa can reduce the locomotor of SHR by the mechanism of down-regulate expression of DAT and up-regulate BDNF.Affiliate Paper Distribution and variations of TCM syndromes in 270 children with attention deficit hyperactivity disorderObjective:To investigate the distributions and variations of TCM syndromes of children with attention deficit hyperactivity disorder(ADHD)in order to provide the evidence for differentiation and treatment of ADHD.Methods:Variations on syndromes of 270 children with ADHD in 9 units were observed and analyzed by SPSS 22.0 software and we summarized the distributions.Results:In 270 newly-diagnosed children,fire hyperactivity of heart and liver syndrome accounted for 40.4%.After treatment,Yin deficiency of liver and kidney syndromes was more common,accounting for 47.8%.According to Diagnostic and statistical Manual of Mental Disorders Fifth Edition(DSM-V),there was a certain link between Western medicine types and TCM syndrome distribution,but there was no significant difference in the syndromes distributions in children with different courses(P>0.05).Conclusion:Syndromes distributions in ADHD correlate with DSM-V types,but not correlates with courses.In the treatment,fire hyperactivity of heart and liver syndrome takes up the most part at initial stage and Yin deficiency of liver and kidney takes up the most part at later stage,which illustrate that ADHD has more excessive syndromes and less deficiency syndromes at first while less excessive syndromes and more deficiency syndromes later,with the tendency of fire hyperactivity of heart and liver syndrome transforming into Yin deficiency of liver and kidney syndrome.