Observation On The Efficacy Of Kaixinjieyu Pill In The Treatment Of Depression And Its Regulation On Neurotrophic Factors

Depression is a common affective disorder.It often manifests as persistent emotional depression,apathy,depression,sleep disorder,loss of appetite,physical discomfort,etc.Severe patients may have anxiety,delusions,hallucinations,extreme grief and other motor agitation and psychiatric symptoms.In recent years,with the increasing pace of social life,the incidence of depression is increasing year by year.Although chemical drugs can produce obvious curative effect,chemical synthetic antidepressants have narrow antidepressant spectrum,high recurrence rate and some serious toxic and side effects after withdrawal.In thousands of years of repeated clinical practice.Chinese medicine has accumulated a large number of effective prescriptions and medicines,which have the characteristics of multi-link,multi-target,integration of body and mind and fundamental treatment principles,and little side effects and no drug dependence.Therefore,in the process of depression prevention and treatment the role of traditional Chinese medicine has attracted more and more people’s attention.Neurotrophic factor(NTF)is a functional small molecule protein secreted by neurons or tissues dominated by neurons.It is closely related to the regulation of differentiation,growth,survival,plas-ticity and regeneration of neurons.It also plays an important role in the growth,differentiation and survival of central and peripheral nervous systems.NTF is an important signal molecule that mediates advanced brain activities(such as cognition,learning,memory,emotion,etc.).It can play a very important role in regulating synaptic structure,synaptic connections,neurotransmitter release in the nervous system.The neurotrophic hypothesis of depressive disorder holds that anti-depressant therapy achieves antidepressant efficacy by supplementing the content of NTFs in the brain.improving synaptic plasticity and inhibiting neuronal apoptosis.It can be concluded that antidepressant therapy may reverse the changes of serum neurotrophic factors cone-entration and expression caused by depression.In this study,the cli-meal efficacy of Kaixinjieyu Pill was evaluated,and the effect of Kaixinjieyu Pill on neurotrophic factors was further explored.Objective:1.Clinical study of Kaixinjieyu Pill in the treatment of depression.1.1 To evaluate the clinical efficacy of Kaixinjieyu Pill in the treatment of depression.1.2 To evaluate the safety of Kaixinjieyu Pill in the treatment of depression.2.Study on the mechanism of Kaixinjieyu Pill in the treatment of depression2.1 To observe the effects of Kaixinjieyu Pill on the levels of glial cell derived Neurotrophie factor(GDNF)and vascular endothelial growth factor(VEGF)in peripheral blood of depressive patients.2.2 To observe the effects of Kaixinjieyu Pill on the levels of glial cell-derived neurotrophic factor(GDNF)and vascular endothelial growth factor(VEGF)in the hippocampus of depressive rats.Method:1.106 patients with depression from September 2017 to February 2019 were randomly divided into Kaixinjieyu pill group and fluoxetine hydr-ochloride group.The treatment group took Kaixin Jieyu Pill(provided by Daxing Preparations Room,Guang’anmen Hospital,Chinese Academy of Traditional Chinese Medicine),4.5g each time,twice a day;the control group took fluoxetine hydrochloride dispersible tablets(Lilai Suzhou Pharmaceutical),20mg/day,in the morning;the treatment course of both groups was 8 weeks.The main observation indicators were Hamilton 24 Depression Score Scale(HAMD-24)and Chinese Medicine Symptom Score Scale.2.Comparison of blood routine and blood biochemistry before and after treatment:The indexes of blood routine and blood biochemical examination before treatment and 8 weeks after treatment:WBC,RBC,HGB.PLT,GLU,BUN.Cr.ALT and AST levels.There was no significant difference between the two groups(P>0.05).and there was no significant change in the levels of each index before and after treatment(P>0.05).3.Among the patients included in the observation,30 patients were randomly selected-including 20 in the treatment group and 10 in the control group.Fasting venous blood samples were taken 5 ml before and in the morning after treatment.The serum levels of GDNF and VEGF were measured by ELISA before and after treatment.4.Thirty six male SD rats were randomly divided into normal group,model group,treatment group and control group.Chronic stress depression rat model was established after 35 days of emergency stimulation.Sugar preference test,open field test and forced swimming test were used to evaluate the antidepressant effect of Kaixinjieyu Pill.5.Enzyme-linked immunosorbent assay(ELISA)was used to determine the changes of GDNF and VEGF in hippocampus of rats before and after treatment.Finally,SPSS 22.0 statistical software was used to process the data,and variance test was used for the counting data(x±s);Chi-square test was used for the counting data:P<0.05 was statistically significant.Results:1.Clinical Research Results of Kaixinjieyu Pill in the Treatment of Depression1.1 Hamilton 24 Depression Score Scale(HAMD-24)results:There were 69 patients in the traditional Chinese medicine group,including 16 cases of clinical control,42 cases of significant effective,2 cases of effective and 9 cases of ineffective,the total effective rate was 86.96%.There were 31 cases in the western medicine group.7 cases of clinical control,14 cases of significant effective,5 cases of effective and 5 cases of ineffective,the total effective rate was 83.87%.At the end of 8 weeks of treatment,the HAMD reduction rate of Chinese and Western medicine group was tested by non-parametric rank sum test.There was no statistical difference between the two groups(t=0.715,P>0.05);there was no statistical difference in curative effect index(t=3.589,P>0.05),suggesting that the antidepression level of Kaixinjieyu Pill was similar to that of fluoxetine hydrochloride.1.2 Results of TCM Symptom Integral Scale:There were 69 cases in Chinese medicine group,19 cases were markedly effective.48 cases were effective,2 cases were ineffective,the total effective rate was 97.10%.There were 31 cases in western medicine group,3 cases were markedly effective,20 cases were effective and 7 cases were ineffective,the total effective rate was 74.19%.T-test showed that there was no difference in symptom improvement and curative effect index between the two groups,suggesting that Kaixinjieyu Pill had the same effective rate as fluoxetine hydrochloride in the treatment of depression.1.3 Safety Assessment100 patients(69 in Kaixinjieyu pill group and 31 in fluoxetine hydrochloride group)who completed the study were examined for blood routine,liver and kidney function and blood sugar before and after 8 weeks of treatment.Data were analyzed by variance analysis and t test,all P values were bilateral test,P<0.05 indicated that there was significant difference.Blood routine,liver and kidney function and blood sugar before and after treatment were compared between the two groups.Blood routine,liver and kidney function and blood sugar indexes before and after treatment for 8 weeks were WBC,RBC,HGB,PLT,GLU,BUN,Cr,ALT and gluten.There was no significant difference in the levels of oxalase(AST)between the two groups before and after treatment(P>0.05).and there was no significant difference in the levels of each index between the two groups before and after treatment(P>0.05).1.4 Determination of serum GDNF and VEGFBefore treatment,the serum GDNF concentration in Chinese medicine group was(393.35±6.91)pg/mL,after treatment,the serum GDNF concentration was(533.64±16.13)pg/mL,with no significant difference(P>0.05);before treatment the serum GDNF concentration in western medicine group was(378.4±6.49)pg/mL,and after treatment,the serum GDNF concentration was(552.38±12.3)pg/mL,with no significant difference(P>0.05).However,the serum GDNF concentration of patients in Chinese medicine group and Western medicine group increased after treatment compared with that before treatmentBefore treatment,the serum concentration of vascular endothelial growth factor in Chinese medicine group was(59.89±5.43)pg/mL,after treatment,the serum concentration of vascular endothelial growth factor was(53.13±5.00)pg/mL,with no significant difference(P>0.05);before treatment,the serum concentration of vascular endothelial growth factor in western medicine group was(62.51±3.62)pg/mL,and after treatment,the serum concentration of vascular endothelial growth factor was(53.33±2.65)pg/mL,with no significant difference(P>0.05).After treatment,the serum levels of vascular endothelial growth factor were higher than those before treatment.However,the serum levels of vascular endothelial growth factor in Chinese medicine group and Western medicine group increased after treatment.2.Study on the mechanism of Kaixinjieyu Pill in the treatment of depression2.1 Improvement of Behavioral Data in CUMS Rats Treated with Kaixinjieyu Pill2.1.1 Weight Changes before and after ModelingThere was no significant difference in the weight of rats in each group before modeling,and the baseline was good.After 35 days of modeling,the weight of rats in model group was significantly lower than that of rats in normal group(P<0.05).The difference was statistically significant(P<0.05),indicating that chronic stress significantly slowed down the weight growth of rats;the weight of rats in each treatment group was significantly different from that in model group(P<0.05).Weight had no significant effect2.1.2 Sugar Water Preference TestAfter 35 days of modeling,the percentage of sugar consumption in model group was lower than that in normal group,with statistical significance(P<0.01):the percentage of sugar consumption in Kaixinjieyu pill group was higher than that in model group,with statistical significance(P<0.05);and the percentage of sugar consumption in fluoxetine hy drochloride group was higher than that in model group,with statistical significance(P<0.05).The results showed that the percentage of sugar and water consumption in the model group was significantly reduced,and Kaixinjieyu Pill and fluoxetine hydrochloride could significantly increase the percentage of sugar and water consumption in the model rats.2.1.3 Test results of forced swimmingThe immobility time of forced swimming in model group was significantly higher than that in normal group(P<0.05);the immobility time of forced swimming in Kaixinjieyu prescription group and fluoxetine hydrochloride group was lower than that in model group,but still higher than that in blank group(P<0.05);the difference was statistically significant(P<0.05);it showed that the imobility time of forced swimming in model rats increased significantly after modeling.Kaixinjieyu Pill and fluoxetine hydrochloride can significantly reduce the immobility time of forced swimming in depression model rats.2.1.4 Open-field test resultsThe distance of open-field test in model group was significantly lower than that in normal group(P<0.01);the distance of open-field test in Kaixinjieyu prescription group was significantly higher than that in model group(P<0.05);and the distance of open-field test in fluoxetine hydrochloride group was significantly higher than that in model group(P<0.05).The results showed that the open-field exercise distance of model rats was significantly reduced after modeling.Kaixinjieyu Pill and fluoxetine hydrochloride could significantly increase the open-field exercise distance of depression model rats.2.2 Determination of GDNF and VEGF in hippocampal area of depression rats2.2.1 Determination of GDNFin hippocampal area of depression ratsThe concentration of GDNF in the hippocampus of the model group was(0.50±0.07)lower than that of the normal group(0.70±0.11).and the difference was statistically significant(P<0.01).The concentration of GDNF in the hippocampus of rats in the traditional Chinese medicine group was(0.66±0.07)higher than that in the model group,and the difference was statistically significant(P<0.01).The concentration of GDNF in the hippocampus of rats in the western medicine group was(0.69±0.10)higher than that in the model group,and the difference was statistically significant(P<0.01).2.2.2 Measurement of vascular endothelial growth factor in hippocampus of depressive ratsThe concentration of vascular endothelial growth factor in the hippocampus of the model group was(57.96±2.73)higher than that of the normal group(47.23±5.83),and the difference was statistically significant(P<0.01).The concentration of vascular endothelial growth factor in the hippocampus of rats in the traditional Chinese medicine group(54.30±4.23)was lower than that in the model group(P<0.05).The concentration of vascular endothelial growth factor in the hippocampus of rats in the western medicine group(54.83±3.05)was lower than that in the model group(P<0.05).Conclusion:1.Clinical Study on Kaixinjieyu Pill in the Treatment of Depression1.1 Kaixinjieyu Pill can improve depressive symptoms and TCM syndromes of patients with depression,and it is an effective prescription for the treatment of depression.1.2 Kaixinjieyu Pill is a safe prescription for the treatment of depression with less adverse reactions and high safety2.Study on the Mechanism of Kaixinjieyu Pill in the Treatment of Depression2.1 Kaixinjieyu Pill can increase the level of GDNF in peripheral blood and decrease the level of VEGF in patients with depression.2.2 Kaixinjieyu Pill can increase the level of GDNF and decrease the level of VEGF in hippocampus of depression model rats.