Effects Of Jianpi Zhidong Decoction On The Expression Of BDNF And The Ability Of Learning And Memory In The Hippocampus Of TS Rats With Chronic Restraint Stress

ObjectiveWe established a rat model of chronic restraint stress Tourette Syndrome(TS),to explore the relationship between the two by examining their learning and memory ability and the expression of brain-derived neurotrophic factor(BDNF)in the hippocampus,and reveal the effects of Jian-Pi-Zhi-Dong Decoction(JPZDD)on learning and memory ability and part of anti-triggered mechanismWith the help of the traditional Chinese medicine inheritance assistant platform system(TCMISS)(V2.5),we conducted data mining on the prescription of Professor Cui Xia in the treatment of pediatric TS in the past three years,and then summarized and analyzed the clinical experience and academic thoughts of the tutor in the treatment of this disease in order to inherit the experience and guide clinical practiceMethods:Animal experiments:The rat model of chronic restraint stress TS was established by IDPN intraperitoneal injection combined chronic restraint stress.Then we tested its learning and memory ability through the Morris water maze experiment,detected the expression of BDNF in hippocampus by real-time fluorescence quantitative technologyClinical studies:The retrospective research method was used to collect and screen out the first prescription of 180 TS children diagnosed by Professor Cui Xia in the Pediatric Outpatient Department of the Third Affiliated Hospital of Beijing University of Traditional Chinese Medicine from January 2017 to December 2019.We established a database with the help of the TCMISS(V2.5),then used data mining techniques,such as frequency analysis,association rule analysis,cluster analysis,to analyze the sexual taste of the prescription,the frequency of use,and the association rules between the medicines.Then we discovered the core drug combination and the new prescriptions for the treatment of TS.Results:1 Results of animal experimentsThe results of stereotyped behavior score:After the 21 days of modeling(the day before medication),compared with the blank group,the stereotype behavior scores of the rats in the model group,western medicine group and traditional chinese medicine group were obviously increased,and the difference was statistically significant(P<0.05);but there was no statistical significance between the model group,traditional chinese medicine group and western medicine group(P>0.05).After 4 weeks of medication:Compared with the blank group,the stereotype behavior scores of the rats in the model group obviously increased,and the difference was statistically significant(P<0.01).Compared with the model group,the stereotype score in western medicine group had a decreasing trend,and the difference was not statistically significant(P>0.05);The stereotype score of rats in traditional chinese medicine group was obviously reduced,and the difference was statistically significant(P<0.05)Experimental results of Morris water maze:In the positioning test,compared with the blank group,the escape latency of the first,second and third days in the model group was obviously prolonged,and the difference was statistically significant(P<0.05).Compared with the model group,the escape latency of the western medicine group and the traditional chinese medicine group had a shorten trend.The shorten trend of traditional chinese medicine group was more obvious,but the difference was not statistically significant(P>0.05).In space experiments,compared with the blank group,the platform quadrant distance ratio and time ratio of the model group was obviously reduced,and the difference was statistically significant(P<0.()5).Compared with the model group.the platform quadrant distance ratio and time ratio of the western medicine group had an increasing trend,but the difference was not statistically significant(P>0.05);The platform quadrant distance ratio of the traditional chinese medicine group increased significantly,and the difference was statistically significant(P<0.05);The platform quadrant time ratio had an increasing trend,but the difference was not statistically significant(P>0.05).The results of BDNF expression in hippocampus:In the blank group(0.99±0.16),the model group(0.81±0.03),the western medicine group(0.88±0.05),and the traditional chinese medicine group(0.96±0.09),there was no statistical significance between the groups(P>0.05)Compared with the blank group,the model group had a decreasing trend,but the difference was not statistically significant(P>0.05).Compared with the model group,the western medicine group and the traditional chinese medicine group had an increasing trend,and the increasing trend of the traditional chinese medicine group was more obvious,but the difference was not statistically significant(P>0.05).2 Results of clinical trialsBasic data of TS children:From 2017 to 2019,out of a total of 180 TS children,136 were males,about 75.56%;44 were females,about 24.44%.A higher incidence of TS among males than among females,approximately 4:1.TS onset age was mainly preschool and school age.The youngest was 4 years old and the oldest was 13 years old,with 9 years of age had the most children.Analysis of prescription medicines:There are 157 chinese medicines in the 180 prescriptions.The four qi of the medicine are mainly warm,cold and calm.Their frequency of use is:1170(43.48%),861(32.00%)and 432(16.05%).The five flavors are mainly spicy,bitter,and sweet,and their frequency of use is:1506(35.07%),1295(30.16%),and 1125(26.20%).The channel tropism of medication is mainly the liver and spleen,and the frequency of use is:1567(24.19%),1076(16.61%);the lung,stomach and heart meridians are followed,and the frequency of use is:882(13.61%),803(12.40%),599(9.25%).There are 30 kinds of medicines with a frequency of 30 and above,and the medicines with a higher frequency are:paeonia lactiflora,radix bupleuri,rhizoma seu radix notopterygii,saposhnikovia divaricata,periostracum cicada,fried fructus gardenia,magnolia,lycopodium clavatum,fructus aurantii,chinese angelica,ligusticum wallichii,ramulus uncariae cum uncis.pueraria lobata,fried atractylodes macrocephalae koidz,bombyx batryticatus,etc.The are closely related and more frequent drug combinations medicines:"paeonia lactiflora,radix bupleuri","paeonia lactiflora,rhizoma seu radix notopterygii","rhizoma seu radix notopterygii,paeonia lactiflora","paeonia lactiflora,saposhnikovia divaricata","paeonia lactiflora,rhizoma seu radix notopterygii,radix bupleuri","saposhnikovia divaricata,rhizoma seu radix notopterygii",etc.Common medicine network diagram showed the core prescription:radix bupleuri,paeonia lactiflora,saposhnikovia divaricata,rhizoma seu radix notoptergii,fructus aurantii,chinese angelica,ligusticum wallichii,fried atractylodes macrocephalae koidz,fried fructus gardenia,ramulus uncariae cum uncis,periostracum cicada,pueraria lobata,lycopodium clavatum,magnolia.We used cluster analysis to mine 9 new prescriptions from 2017 to 2019,12 new prescriptions in 2017,8 new prescriptions in 2018,and 6 new prescriptions in 2019.These are the more meaningful prescriptions obtained through clinical analysis:①paeonia lactiflora,fructus aurantii,radix bupleuri,peppertree pricklyash,asarum,rhizoma zingiberis;②codonopsis pilosula,chinese-date,mangnolia officinalis,pinellia ternata;③rhizoma seu radix notopterygii,saposhnikovia divaricata,fried fructus gardenia,golden cypress,cassia twig;④inula nervosa wall,ginger,mangnolia officinalis,lycopodium clavatum;⑤radix glycyrrhizae preparata,bombyx batryticatus,periostracum cicada,radix curcumae,alpinia katsumadai;⑥rhizoma seu radix notopterygii,fried fructus gardenia,magnolia,peppertree pricklyash,dark plum,golden cypress.Conclusion:The rat model with chronic restraint stress TS may have impaired learning and memory ability,and JPZDD can resist the influence of emotional factors,improve their learning and memory ability and obviously decrease the stereotyped movement of rats.Whether JPZDD achieved by up-regulating the expression of the BDNF mRNA in the hippocampus remains to be further explored.Professor Cui Xia is good at treating pediatric TS by activities of qi.The syndrome type of TS is mainly spleen deficiency and liver hyperactivity.She uses JPZDD to support soil and inhibit wood,and soothe the liver;She uses sini powder to reduce pathogenic factors and relieve depression,and harmonize liver and spleen;She uses shengjiang powder to depress the heat,regulate the qi;She uses wumei pills to coordinate yin and yang,soften the liver and relax the wind.In clinical practice,"it is alaways important to regulate the qi activity",and the diaphanous thought runs through it.The three methods of relieving liver qi,reducing liver fire,and relaxing liver wind are used flexibly to restore the body and function of the liver.Although she pays attention to liver wood,she does not forget spleen soil.She is good at using the four qi of medicine to correct the abnormality of the rise and fall of qi,attaching importance to the meridian of medicine,and making good use of wind medicine.