Analysis Of The Intervention Effect And Mechanism Of Jingning Granules On Hyperactive Behavior And Attention Deficit Disorder In ADHD Model Animal

Children with attention deficit hyperactivity disorder(attention deficithy peractivity,ADHD),that is,compared with children of the same age,there are obvious hyperactivity,impulsivity,learning or memory disorders of a group of syndromes(disorder).ADHD is a common mental disorder in children[1].ADHD is usually 6 years old before onset of[2],about 70%of the children in adolescence still have obvious symptoms,1/3 can be extended to adulthood.The interaction between the children and the adults often has the performance of inhibition,the lack of normal caution and restraint,the specific delay of cognitive,motor and speech development,and the subsequent social disorder and inferiority.Therefore,domestic and foreign scholars pay more and more attention to the research of ADHD.Methylphenidate hydrochtoride for the treatment of this disease commonly used drugs,the drug short-term effect is significant,but the side effects,and[3]is contraindicated in children under the age of 6,so the development of traditional Chinese medicine preparation is very important for the safety of long-term growth and development in the period of the children become.1.Research on ADHD modelObjective:To observe the effect of Ritalin on the behavior and dopaminergic neurons in the brain of SHR rats,so as to evaluate the rationality of SHR rats as an animal model of ADHD.Methods:The spontaneously hypertensive rats(spontaneously hypertensive,rats,SHR)as a model of rat ADH D,using Ritalin(6.75mg/kg,3.375mg/kg)for 17 day treatment,the WKY rats in control group,routine feeding.The spontaneous activity of SHR rat moving distance,moving rate,open box center area cumulative time,vertical accumulation time and five stage test of attentional set transfer task behavior in error rate,error number,the number of mining,moving distance,the parade of Morris water maze speed,high speed time and the total time parade parade.Social Interaction Test Pinning index and Pouncing times of behavior;using PCR and Western Blot method for the determination of rat prefrontal cortex,striatum,DRD2 gene and DRD1 receptor expression level,to observe the effect of Ritalin on the behavior of SHR rats and dopaminergic neurons in SHR rats,to explore the rationality of ADHD as animal model.And the selection of test methods for the evaluation of drug efficacy.Results:(1)the results of autonomic activity:SHR rats’ moving distance,moving speed,the cumulative time of the open center area,the cumulative time of body stretch were significantly higher than that of WKY rats(P<0.05).Each dose of Ritalin could reduce the migration distance,the moving rate and the cumulative time of the central area of SHR rats,but there was no significant difference between the two groups.(2)rats task attentional set shifting behavior results:compared with normal control group,SHR rats in the stage of simple discrimination(SD),(CD),identify the complex stage within dimension conversion stage(IDS)and outer dimension conversion stage(EDS),the number of errors,the error rate was increased with the number of mining;comparison with the model group,Ritalin administered continuously for seventeen days,each dose can reduce the error in a rat model of frequency,the number of mining,error rate,improve attentional set shifting defects in SHR rats.(3)The results of Morris water maze showed that the moving distance,the marching speed,the high speed marching time and the total marching time of SHR rats were significantly higher than those of WKY rats(P<0.05).Different doses of Ritalin can reduce the total length of the target quadrant,the marching speed,the high speed parade time and the total parade time in SHR rats,but there was no significant difference compared with the model group.(4)Social Interaction Test results:the results showed that the number of times of Pinning and Pouncing of SHR rats were significantly higher than those of WKY rats(P<0.05).Different doses of Ritalin could reduce the number of Pinning and Pouncing times of rats in different degrees,but there was no significant difference compared with the model group(SHR).(5)PCR showed:DRD1 striatum of the rats in the model group,the prefrontal brain,reduced in different degrees relative content of DRD2 mRNA were compared with WKY rats,the DRD1 in the striatum,the relative content ofDRD2 mRNA decreased significantly(compared with the model group,P<0.05).The dose of Ritalin could increase the relative content of DRD1 and DRD2 mRNA in prefrontal cortex and striatum of rats in different degrees,but there was no significant difference between SHR and model group.(6)the results of Western Blot showed that the expression of DRD1,DRD2 and DAT in prefrontal cortex and striatum of SHR rats were significantly lower than those of WKY rats(P<0.01).The DRD1 and DRD2 expression in the prefrontal cortex and striatum of the SHR rats were significantly increased in all doses of Ritalin(P<0.05)compared with the model group.Conclusion:(1)Ritalin can improve SHR rats hyperactivity,impulsivity,learning and memory impairment,cognitive impairment and other behavioral abnormalities(2).SHR rats can be used as ADHD model rats.2.Effect of Jingning Granule on behavior of ADHD model ratsObjective:To observe the effect of Jingning Granule on the behavior of ADHD model rats,and to evaluate the efficacy of Jingning granules.Methods:The spontaneously hypertensive rats(spontaneously hypertensive,rats,SHR)as attention deficit hyperactivity disorder(attention deficit hyperactivity disorder,ADHD)of the rat model,the particles(20.25g/kg,10.125g/kg,Jingning 5.0625g/kg),Methylphenidate HC1 Extended-release Tablets(6.75mg/kg)and pediatric Huanglong granule(0.9375g/kg)administered continuously for 17 days for treatment,and normal control group,normal feeding.The independent activity of rat model of ADHD moving distance,moving speed,open field center regional activity duration,the cumulative time lengthening of the body and the five stage attentional set shifting behavior in task ADHD model rats,3min latency and error times the total number of mining and so on behavioral indicators,efficacy evaluation of Jingning particles.Results:(1)autonomic activity behavior of rats.Results:compared with normal control group,rat model of moving distance,moving speed,open box center area cumulative time,lengthening of the body total time increased significantly(P<0.05,P<0.01);compared with the model group,Jingning particles after seventeen days of medication,the the dose can significantly reduce the moving distance,moving speed,open box center area cumulative time,lengthening of the body total time(P<0.05,P<0.01),improve the ADHD rat model of hyperactivity and anxiety symptoms;(2)rats to study attentional set shifting task results:compared with normal control group,model the rats in the stage of simple discrimination(SD),(CD),identify the complex stage within dimension conversion stage(IDS)and outer dimension conversion stage(EDS)latency was significantly shortened(P<0.05),the number of errors,the total number of all mining 3min Increased;compared with the model group,Jingning particles after seventeen days of medication,the dose can prolong the incubation period,rats in model rats,reduce error number 3min the total number of mining,improve the attentional set shifting defects of ADHD model rats.Conclusion:(1)Jingning granule can improve the behavior of ADHD modelrats abnormal;(2)with attentional set shifting defects of ADHD model rats;Jingning granules can effectively improve the attentional set rat model of ADHD metastasis.3 Jingning Granule on brain dopamine neurons of the rat model of ADHDObjective:To observe the effect of Jingning Granule on brain dopamine neurons of the rat ADHD model,to evaluate the efficacy of particles in Jingning.Methods:the spontaneously hypertensive rats(spontaneously hypertensive,rats,SHR)as attention deficit hyperactivity disorder(attention deficit hyperactivity disorder,ADHD)of the rat model,the particles(20.25g/kg,10.125g/kg,Jingning 5.0625g/kg),Methylphenidate HC1 Extended-release Tablets(6.75mg/kg)and pediatric Huanglong granule(0.9375g/kg)administered continuously for 17 days of treatment,the other.The normal control group,normal feeding.The contents of DA and HVA in the prefrontal cortex of rats were determined by HPLC-ECD method.The DRD1,DRD2,DAT gene and the expression of Blot were measured by PCR and Western.Results:(1)HPLC-ECD results:the content of DA in the prefrontal cortex and striatum of SHR rats was significantly lower than that of WKY rats(P<0.05).The content ofHVA in the prefrontal cortex and striatum of SHR rats was significantly higher than that of WKY rats(P<0.05).The dose of particles can increase the content of DA in the prefrontal cortex and striatum of SHR rats,and the dose of particles can reduce the content of HVA in the prefrontal cortex and striatum of SHR rats.(2)PCR Results:DRD1 in prefrontal cortex,brain in model group rats,reduced in different degrees relative content of DRD2 mRNA were compared with WKY rats,the DRD1 in the striatum,the relative content of DRD2 mRNA decreased significantly(compared with the model group,P<0.05).Jingning granule 20.25 g/kg could increase the relative content of DRD1 and DRD2 mRNA in the prefrontal cortex and striatum of rats in different degrees,but there was no significant difference between the SHR group and the model group.(3)Western Blot results:the expression of DRD1,DRD2 and DAT in the prefrontal cortex and striatum of SHR rats were significantly lower than those of WKY rats(P<0.01).Jingning granule can obviously increase the dose of SHR in rat brain striatum,prefrontal cortex,DRD1 DRD2 expression(compared with the model group,P<0.05);Jingning particles in different dosages can increase the expression of DAT protein in rat prefrontal SHR(compared with the model group,P>0.05);Jingning,20.25 particle 10.13g/kg significantly increased in SHR rats the frontal lobe of the brain,DRD1 and DRD2 protein expression in the striatum(compared with model group,P<0.05),Jingning 20.25g/kg particles can significantly increase the expression of DRD2 protein in SHR rat striatum,prefrontal cortex(compared with model group,P<0.01);Jingning 20.25g/kg particles can significantly increase the expression of DAT protein in rat prefrontal cortex(with SHR compared with model group,P<0.01).Conclusion:the mechanism of the improvement of abnormal behavior of ADHD rats may be related to the expression of DRD1,DRD2,DATmRNA and DRD1,DRD2,DAT receptor in the prefrontal cortex and striatum of rats with elevated ADHD.