Effect Of Jiawei Sini San On Behavior And HPA Axis Of Depressed Adolescent Rats Model With Stress

Literature research and theory discussionAdolescent depression is common adolescent mental disorders,which belongs to the traditional Chinese medicine "melancholia" category of emotional diseases.Corrent incidence of youth depression is rising.Adolescence depression is not only harm to young people' s mental health,the harm may also persist into adulthood and even whole life process.Its pathogenesis has not been completely clear,and the medicine can be used for the treatment of adolescent depression is less effective and have side effects.Related studies suggest that adult mental disorder was not only the instant effect of stress,but often associated with life stress of early stage(youth stage)closely.So stress is an important cause of depression and other mental disorders.This study suggested that adverse stimulation resulted from the rapid development of social,adverse experience in the early stages of life(lack of maternal love)and susceptibility to adverse childhood or youth itself were the main source of adolescence depression and other mental disorder diseases.These early life adverse experiences(stress factors)increased the incidence rate of mental disorders in adolescents or children.Traditional Chinese Medicine(TCM)holds that the liver had a function of regulating emotion.Based on this theory,it has achieved good curative effect in treating emotional disease from the liver.Because of adolescence belongs to "children" stage of TCM,so it had the physiological and pathological characteristics of liver in children.This study suggests that children with "liver often than" not only refers to the pathological disease easily from the cremation,should also include the youth period easy to estrus and close to the liver disease,"the liver often more "is the basis of adolescence depression,the relationship between adolescence depression and the liver was closely.At present,the experimental study on emotional diseases based on psychological stress of modern medicine,dysfunction of liver caused by psychological stress can be expressed as overacfivity of the hypothalamic pituitary adrenal axis(HPA)and a series of functional disorder in neuroendocrine responses.The liver is the core of the reaction of psychological stress.The study found that traditional Chinese medicine can improve the mental stress caused by emotional disorders and has some antidepressant effect.Therefore,this study imitated the contemporary social environment which might cause adolescence depression in adolescents and children by chronic unpredictable stress(CUMS)and maternal separation simulation,and tried to establish adolescence stress depression model which is more fit with the theory of traditional Chinese medicine.The study used the liver flavored the formulas of TCM intervention Jiawei Sini San to explore the way to replicate depression animal model and its pathogenesis mechanism,to promote the research of the central mechanism of liver,to provide theoretical basis and experimental basis for the effective prevention and treatment of teenage period depression by TCM.Experimental research1.Effect of Jiawei Sini San on Behavior and HPA axis of Depressed Adolescent Rats Model with StressIn the study,we established the animal moldes on 21-day-old wistar rats by the choice of adolescent chronic unpredictable stress method on wistar rats,and using Tiaogan prescription—Jiawei Sini San as intervention to observe the change of rats behavior and HPA axis.It turns out:(1)Sucrose preference Compared with the control group,preference of sugar model rats showed a decreasing trend during the first to 28th day,on the 28th days was significantly lower(P<0.01),sucrose preference of fluoxetine group tended to decrease during 7-21 days,and on the 14th was significantly lowe(P<0.05);sucrose preference in Jiawei Sini group on the 7th,14th day were significantly decreased(P<0.01),increased on the 28th day,no significant difference compared with control group(P>0.05).(2)Weight The weight of rats in each group had no significant difference(P>0.05)before the stress was given.Begain with the stress,the control group showed a rising on weight gain,while the other three groups declined in the 21th and 28th day;compared with the control group,stress group decreased on weight gain significantly(P<0.05),suggesting stress had great effect on weight gain.Compared with stress group,fluoxetine group weight increased significantly on the 14th and 21th day(P<0.05),JWSNS was significantly slow in the 7th and 21th day(P<0.05).(3)Open-field test Compared with the control group,stress group activities in the Central time zone decreased significantly(P<0.01),while the total distance,average speed were not significant changed after the stress(P>0.05).Compared with the model group,the central odometer of fluxetine group and JWSNS group had a trend of increase.(4)ACTH and CORT content Compared with the control group,plasma ACTH the stress group was higher(P<0.05),CORT levels was significantly higher(P<0.01).Compared with the stress group,plasma ACTH and serum CORT content of fluoxetine group and JWSNS were significantly reduced(P<0.05);compared with the fluoxetine group,the content of plasma ACTH and CORT of JWSNS group was higher,but had no significantly difference between(P>0.05).2.Effect of maternal separation on HPA axis of adolescent rats during adolescent time96 one day-old Wistar rats(male and female were equal number)were randomly for maternal separation group(MS)and the control group,48 rats in each group(male and female were equal number).Maternal separation group rats subjected to 3 hours daily maternal separation stimulation from PND1 to PND21,the control group without any interference,the two groups of rats were weaned on PND21 day,after the day all rats were kept without any stimulation.We detected the serum ACTH and CORT concentration and CRH content respectively on PND21,PND28,PND35,PND42,PND49,PND56.The results were found:(1)Compared with the control group,serum ACTH and CORT concentration and content of hypothalamic CRH of MS group rats respectively on PND21,PND28,PND35,PND42,PND49,PND56 showed no significant difference(P>0.05).(2)On PND49,serum ACTH concentration of control group female rats was significantly higher than that of male rats(P<0.01).On PND28,PND49,PND56,CORT concentration of control group female rats were significantly higher than that of male(P<0.05).The concentration of serum ACTH in group MS female rats on PND21,PND49,PND56 was significantly higher than that of male rats(P<0.05);serum CORT concentration of MS group male female rats on PND21,PND28,PND35,PND42,PND49,PND56 showed no obvious difference respectively(P>0.05).On PND21,compared with the male rats of control group,MS group increased significantly(P<0.05).(3)Serum ACTH concentrations of control group on PND21 to PND56 with' showed large fluctuation over time,the concentration of serum ACTH of rats in the MS group was also volatility,but the volatility is not obvious.Serum CORT concentration and CRH content of the control group and MS group rats both showed obvious fluctuation over the time of youth period.3.Effect of Jiawei Sini San on the behavior and HPA axis of depressed adolescent rats model with mutiple stress24 one day-old Wistar rats(male and female)were randomly divided into control group,model group,Jiawei Sini Powder group(JWSNS),8 rats in each group(male and female).The stress group and JWSNS group rats were received 4 hours daily maternal separation from PND1 to PND21 and treated with chronic unpredictable stress model(the same way as the experimental one)from PND29 to PND 56.JWSNS group were gavaged with the Jiawei Sini San every day from PND29 to PND 56,stress group and blank group were gavaged with normal saline.The control group rats were normal fed without any stimulation.All the rats were weaned on PND21.Sucrose preference,body weight,open field test,serum ACTH and CORT concentration were measured on PND56.The results found:(1)Weight and sucrose preference Compared with the control group,the weight and sucrose preference of mutiple stress group rats were significantly decreased(P<0.01).Compared with the mutiple stress group,JWSNS rats weight increased,the difference was not statistically significant(P>0.05),but sucrose preference JWSNS group of rats was significantly increased(P<0.01).(2)Open field test Compared with the control group,the activity and the total distance of rats mutiple stress group were significant declined(P<0.01),and the total distance in the central region is significantly reduced(P<0.05).Compared with the mutiple stress group rats,activity of JWSNS rats was significantly increased(P<0.01),the central region of time,distance and total distance of the central region had a trend of increase.(3)Serum ACTH and CORT concentration Compared with the control group,serum ACTH concentration of mutiple stress group rats increased significantly(P<0.01),CORT concentrations were increased(P<0.05).Compared with the mutiple stress group,JWSNS rat serum ACTH concentrations were significantly decreased(P<0.05)and CORT concentrations tended to decrease.Conclusion(1)Both chronic unpredictable stress and maternal deprivation stress combined with chronic unpredictable stress can effectively induce depression in adolescence rats.The depressed adolescence rats showed depression like behavior and neuroendocrine function disorder,both the methods can be used to replicate depressed animal mode of adolescence rats successfully.(2)In nature,HPA axis of rats during adolescence was dynamic fluctuating.And the serum ACTH,CORT concentration and CRH content in the hypothalamus of female rats showed a trend of higher than male rats.It suggested that adolescent female rats are more easily affected by adverse stimulus.HPA axis of the adolescence rats which experienced maternal deprivation stress may not show significant changes,it may result from the inhibition state of HPA in stressed rats.(3)Jiawei Sini Powder which has the function of regulate the "live" can significantly improve behavior and the disorder of the nerve endocrine of HPA axis in depressed adolescent rats.It has an antidepressant effect.