The Clinical Curative Effect Observation And Research On Mechanism Of Action Of The Therapy Of "Nourishing Yin,Clearing Heat And Harmonizing Stomach" In The Treatment Of Insomnia

1.Literature researchThe graduates' dissertation reviews the knowledge of traditional Chinese medicine on insomnia from the name of disease,etiology and pathogenesis,etc;summarizes the rule of TCM syndrome of insomnia,modern therapy of traditional Chinese medicine and general situation of prescription research;analyzes the problems and research directions existing in the Chinese medicine treatment of insomnia;introduces the definition,epidemiology,pathophysiology,treatment progress and existing problem of western medicine for insomnia.2.Clinical research2.1 Analysis of the regularity of the pathogenesis and the prescription of insomnia patients2.1.1 Research purposesStudied the gender,age,differentiation of symptoms and usage characteristics of medicine of insomnia patients through the study of outpatient insomnia patients of the First Affiliated Hospital of Guangzhou University of traditional Chinese medicine during January 2012 to December 2014 retrospectively.Further more,finded out the occurrence rule of insomnia in order to guide the clinical medication and build for scientific research in the future.2.1.2 Content and methodsIn this study,age structure/sex ratio and the characteristics of the used Chinese medicine were mainly counted.Analysised characteristics and influencing factors of insomnia patients in nearly three years in Lingnan area(First Affiliated Hospital of Guangzhou University of Chinese Medicine),explored characteristics of TCM prescription and drug used,summed up the main therapeutic methods.2.1.3 FindingsA total of 18839 patients were enrolled(the same patient using the same prescription at different times was treated for one medical examination),the youngest was 18 years old,the oldest was 99 years old,and the average age was 14.18+43.32 years old.Insomnia is higher in 21-60 years old and women.485 Chinese medicines were used in 18839 prescriptions,275 Chinese medicines were used less than 100 times,and 71 Chinese medicines were used more than 1000 times,such as licorice,semen zizyphi spinosae,Poria cocos,Radix Paeoniae Alba,Caulis Polygoni Multiflori,Radix Bupleuri,Rhizoma Atractylodis Macrocephalae,Albizzia julibrissin,etc,and can be classified for clearing heat,nourishing Yin,eliminating phlegm.and harmonizing stomach,promoting qi circulation and removing obstruction in the collateral,soothe the nerves,tonifying Qi and warming Yang,activating blood and nourishing the blood,expelling wind etc.Suanzaoren Decoction,Baihe Dihuang Decoction,Liuweidihuang Pill,Erzhi Pill,Wendan Decoction etc,were common used in the treatment of insomnia.2.1.4 ConclusionMost insomnia patients aged between 21-60,and more patients are females.Because of the pressure of life,work and physiology,diet and other reasons,people are more prone to appear Yin deficiency and Yu heat syndrome.Through the analysis of the prescription for insomnia,we can see that:The most commonly used treatments for insomnia are "clearing heat and nourishing Yin,resolving phlegm and stomach-harmonizing,liver solution Yu heat,nourishing Yin and nourishing blood,promoting blood circulation to remove blood stasis,harmonic Ying and Wei",etc.Nourishing yin medicine with highest frequency in medicines of treatment deficiency syndrome,and nourishing blood medicine take the second place.Resolving phlegm and reconcile the stomach medicine,jieyuxingqi and clearing heat drugs are most commonly used in excess syndrome.2.2 Clinical observation of the clinical therapeutic effect of the method of "nourishing yin,clearing heat and harmonizing stomach" in the treatment of insomnia.2.2.1 Research purposesObserve the clinical effect about Nourishing yin and clearing away heat and reconcile stomach(Zaorenshenan Decoction)in treatment insomnia of Yin deficiency and Yuheat syndrome.2.2.2 Research methodCollection 43 insomnia patients met the inclusion criteria,Using general situation questionnaire,Pittsburgh sleep quality index scale(PSQI)and TCM symptoms questionnaire of evaluation of drug efficacy and drug safety observation before and after treatment,and statistical processing and analysis of the observed indicators.2.2.3 Research results2.2.3.1 Comparison of PSQI component score and total scoreUsing PSQI survey before and after treatment,it was found,sleep quality,sleep time,sleep efficiency,sleep disorders,daytime function and total score have significant difference in comparison(P<0.05 or P<0.05)before and after used study medication.2.2.3.2 Comparison of main symptoms of TCMAfter treatment with Zaorenshenan Decoction,Patients improved their sleepness significantly in sleep quality,the degree and frequency of difficulty in falling asleep,festless sleep or early awakening,dreaminess,spiritlessness,sleepiness(P<0.01),Indicating that Zaorenshenan Decoction can obviously improve the sleep quality of patients.2.2.3.3 Observation of the effect of TCM symptoms before and after the study of the object of studyAfter treatment with Zaorenshenan Decoction,the total effective rate was 90.70%in TCM symptoms,indicate the clinical effect is good.2.2.3.4 The results of clinical curative effect were determined before and after treatmentAccording to the effect criteria of the Chinese medicine treatment of insomnia clinical trial guiding principles(first series),8 cases were cured,markedly effective in 14 cases,effective in 16 cases,invalid 5 cases,the total efficiency 88.38%in 43 cases.2.2.4 conclusionPatients with Zaorenshenan Decoction treatment,PSQI component scores were significantly reduced compared with those before treatment,indicating that patients with improvement in sleep quality,sleep latency,total sleep time,sleep efficiency,sleep disorders and daytime function,especially in the quality of sleep,sleep time,sleep disorders,daytime function effect is obvious(P<0.01),in terms of total sleep time and sleep efficiency improved(P<0.05).After treatment,yin deficiency and stagnated heat type of insomnia symptoms include symptoms factor scores compared with before treatment,decreased significantly(P<0.01),patients with spirit fatigue body tired,dream,difficulty falling asleep,easy wake up and other symptoms have improved significantly.By nimodipine method in evaluation of curative effect,Zaorenshenan Decoction for treating yin deficiency and stagnated heat syndrome in patients with clinical effective rate reaches 88.38%and syndromes of TCM to improve the total effective rate was 90.7%.The research shows that Zaorenshenan Decoction based on the method of“nourishing yin,clearing heat and harmonizing stomach" for yin deficiency and stagnated heat.type insomnia patients with good clinical efficacy,worthy of further study.3.Experimental study3.1 Research purposesThe paper discusses the mechanism of Zaorenshenan Decoction through the establishment of insomnia model of rats and to observe the effect of Zaorenshenan Decoction to insomnia rats brain neurotransmitters of the central nervous system.3.2 Research method60 male SD rats were randomly divided into three groups:blank control group,model group,Zaorenshenan Decoction high dose group,Zaorenshenan Decoction middle dose group,Zaorenshenan Decoction low dose group and diazepam group,10 rats in each group.Except the blank group,other groups using rat model of insomnia para chlorophenylalanine(PCPA)production,after successful modeling,the blank control group and model group were given distilled water gavage;Zaorenshenan Decoction low,middle and high dose group given Zaorenshenan Decoction intragastric administration;stability and control group was treated with valium suspension gavage;given stomach for 10 days,1 times per day.3.3 Detection indexRat hippocampal glutamate(Glu)and gamma aminobutyric acid(GABA)content,expression of hippocampus of rats of 5 hydroxytryptamine(5-HT),rat hypothalamus cholecystokinin-8(CCK-8)expression.3.4 conclusion3.4.1 Effect of Zaorenshenan Decoction to glutamic acid of insomnia rat HippocampusAfter PCPA modeling,the content of Glu in the hippocampus of rats after insomnia was significantly higher(P=0.000).Drug intervention,Zaorenshenan Decoction high dose group,Zaorenshenan Decoction middle dose group and diazepam group of Glu content decreased significantly,significantly lower than the model group(P=0.000),and high dose group and blank control group had no significant difference(P>0.05);Zaorenshenan Decoction high dose group and middle dose group,the difference was not obvious(P>0.05),but are better than low dose group(P=0.000).The results indicated that,PCPA insomnia caused the mechanism may be are related to excitatory amino acids Glu content increased in hippocampus of rats,Zaorenshenan Decoction can achieve the effect of anti insomnia from reduce the content of Glu;Zaorenshenan Decoction reduce insomnia rats hippocampus Glu content may be associated with the dose.3.4.2 Effect of Zaorenshenan Decoction to gamma aminobutyric acid of insomnia rat HippocampusAfter PCPA modeling,the content of GABA in the hippocampus of insomnia rats was significantly decreased(P=0.000).After drug intervention,Zaorenshenan Decoction high dose group,middle dose group,diazepam group GABA content increased significantly,significantly higher than the model group(P=0.000),but still lower than the blank control group(P=0.000).Zaorenshenan Decoction high dose group of GABA content and middle dose group compared with significant difference(P=0.002),middle dose group was superior to low dose group(P=0.000).The content of GABA between high dose group and diazepam group is no significant difference(P>0.05).The results indicated that,the mechanism of insomnia caused PCPA may caused by inhibition of GABA content decreased in the hippocampus of rats,and Zaorenshenan Decoction can increase GABA content,and its effect was correlated with the dose of drug,the effect is same to diazepam when drug reached a certain concentration.3.4.3 Effect of expression of 5-HT in hippocampus of insomnia rats by Zaorenan DecoctionHippocampus 5-HT of insomnia rat caused PCPA positive expression and the integral optical density values significantly decreased(P=0.000,<0.05).Compared with the model group,diazepam group and Zaorenshenan Decoction high,medium and low dose group can significantly improve the hippocampus 5-HT positive expression and the integral optical density value(P=0.000),and can reach the level of the blank group(P>0.05),5-HT positive cells expression rate of high dose group are higher than that of the blank control group and the diazepam group(P=0.000,P=0.003).Hippocampus 5-HT integral optical density value and positive expression rate of Zaorenshenan Decoction high dose group is different to low dose group(P=0.019,P=0.000),suggesting that therapeutic effect may be correlated with the drug concentration.3.4.4 Effect of Zaorenshenan Decoction on CCK-8 expression in hypothalamus of insomnia ratsThe contents of CCK-8 in hypothalamus of rats induced by PCPA were significantly decreased(P=0.000).Zaorenshenan Decoction high dose group,medium dose group,low dose group and diazepam group were significantly increased the content of CCK-8 in hypothalamus of insomnia rats(P=0.000,P=0.000,P=0.001,P=0.000,<0.05).Zaorenshenan Decoction high dose group content of CCK-8 was higher than that of medium dose group,the difference is statistically significant(P=0.000).Zaorenshenan Decoction medium dose group content of CCK-8 was higher than that of low dose group,the difference between the two groups has statistical significance(P=0.000).Results suggest that Zaorenshenan Decoction may through upregulate the content of CCK-8 in hypothalamus of insomnia rats so as to improve sleep,Zaorenshenan Decoction promote CCK-8 release effect is concentration dependent,and the mechanism is the same as diazepam.3.5 ConclusionIn summary,the mechanism of Zaorenshenan Decoction in the treatment of insomnia may and blocked the excitatory amino acid glutamate release,promote inhibitory amino acid GABA release,increase the content of 5-HT in the brain,and increased expression of CCK-8 in hypothalamic and to achieve dynamic balance,by inhibiting the awakening and excitement,promote sleep,regulating the sleep wake cycle,play a sedative and hypnotic effect.