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Effect Of Xiao-Yao-Jie-Yu-San On BDNF In VTA-NAc Pathway Of PSD Rats And Its Clinical Application

Posted on:2020-04-03Degree:DoctorType:Dissertation
Country:ChinaCandidate:C D WangFull Text:PDF
GTID:1364330647955948Subject:Internal medicine of traditional Chinese medicine
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Objective: To observe the effect of xiao-yao-jie-yu-san on serum BDNF and Hamilton depression scale scores of patients with post-stroke depression,and to study the clinical effect and mechanism of xiao-yao-jie-yu-san on patients with post-stroke depression.To observe the effect of xiao-yao-jie-yu-san on the behavior of rats with post-stroke depression and the expression level of BDNF in the VTA-NAc pathway,and to explore the biological mechanism of xiao-yao-jie-yu-san in the treatment of post-stroke depression.Methods: part Ⅰ: 70 patients who met the diagnostic criteria of traditional Chinese and western medicine and belonged to liver depression and spleen deficiency were selected,and divided into two groups with 35 patients in each group by random number table method.Both groups were given conventional basic medical treatment in western medicine,and the treatment group was treated by xiao-yao-jie-yu-san at the same time,and the control group was also treated by fluoxetine capsules.Both groups were treated for 28 days.The serum BDNF,HAMD-17 score and safety observation indexes of the patients were observed before treatment and 28 days after treatment.Part Ⅱ : The PSD rat model was established by the middle cerebral artery embolization(MCAO)and chronic unpredictable mild stress(CUMS)method(CUMS)combined solitary raise,and sixty SD male rats were randomly divided into6 groups included control group,MCAO model group,MCAO+CUMS model group,the PSD+fluoxetine group(1.84mg/kg/d),the PSD+low-dose of xiao-yao-jie-yu-san group(450mg/kg/d),the PSD+high dose of xiao-yao-jie-yu-san group(900mg/kg/d),there are 10 rats in each group.The drug group was given 2m L of the corresponding solution by gavage,and the other groups were given 2m L of distilled water of equal volume daily by gavage,each group was given gavage for 4 weeks.We should record the weight of rat,force swimming test,sugar water preference test during the tria.After the experiment,the BDNF content in brain tissue was detected by enzyme-linked immunosorbent assay(ELISA),and the BDNF protein expression level in brain tissue was detected by Western Blot.Results: part Ⅰ: 1.The Hamilton depression scale score of the treatment group and the control group after treatment was lower than that before treatment(P<0.05).Aftertreatment,the difference between the treatment group and the control group was statistically significant(P<0.05).2.The differences of serum BDNF in the concentration was not statistically significant for two groups of patients before treatment(P>0.05),Compared with before treatment,the level of serum BDNF of the two groups after treatment in patients was increased significantlly(P<0.05).The serum BDNF levels in both groups after treatment was not statistically significant(P>0.05),but plasma BDNF concentration levels of the treatment group patients was elevated significantlly than control group obviously(P<0.05).PartⅡ: 1.Forced swimming test: before administration,the immobility time of PSD rats in each group was significantly increased and the struggle time of PSD rats in each group significantly decreased compared with the blank group(P<0.01).After treatment,the struggle time of rats in the fluoxetine group was significantly longer than that in the model group(P<0.01).Compared with the model group,the immobility time of the rats in the low and high dose groups were significantly reduced and the struggle time were significantly increased(P<0.01).Compared with fluoxetine group,there was no significant difference in the immobile time of rats in the low-dose group(P>0.05),while the struggle time of rats in the low-dose group was longer than that in the fluoxetine group(P<0.05).Further comparison between the low and high dose groups of traditional Chinese medicine showed that the inactivity time of rats in the high dose group decreased and the struggle time increased(P<0.01).2.Sugar water preference test: before administration,the consumption of sugar water in PSD rats in each group was reduced compared with that in the blank group(P<0.05).After treatment,the consumption of sugar water increased in the low-dose and high-dose groups of xiao-yao-jie-yu-san and the fluoxetine group compared with the model group(P<0.05),suggesting that the above three groups are effective in drug treatment.In addition,the increase of sugar water consumption was particularly significant in the high-dose group of traditional Chinese medicine and the fluoxetine group,and there was no statistical difference between the two groups(P>0.05),suggesting that the high-dose group of xiao-yao-jie-yu-san had the same efficacy as the fluoxetine group.There were statistically significant differences between the two groups(P<0.05).3.ELISA results of BNDF in brain tissues showed that the level of BNDF in VTA-NAc in MCAO group and PSD group was significantly lower than that in sham group(P<0.01).Similar to the rats treated with fluoxetine,the content of BNDF in VTA-NAc tissues was significantly increased in both high and low dose of the xiao-yao-jie-yu-san groups(P<0.01).4.Protein expression of BNDF in brain tissues of rats with post-stroke depression:After MCAO and MCAO+CUMS operation,BNDF expression was sharply down-regulated compared with that of rats in the sham group(P<0.01).The BNDF expression in VAT-NAc tissues of PSD rats was significantly up-regulated in both the fluoxetine group and the high and low dose of and xiao-yao-jie-yu-san group(P<0.01).Conclusion:1.Xiao-yao-jie-yu-san and fluoxetine capsule have improved the efficacy of patients with post-stroke depression,but the efficacy of xiao-yao-jie-yu-san is better than fluoxetine capsule in improving the depressive symptoms of patients.Both of them can improve the serum BDNF concentration of patients with post-stroke depression and reduce the HAMD-17 score of Hamilton depression scale,but xiao-yao-jie-yu-san can improve the serum BDNF extent and reduce the hamd-17 score of patients more obviously,and the clinical effect is better than fluoxetine capsule.2.Xiao-yao-jie-yu-san can improve the expression of BNDF in the hippocampus and cortex of brain tissue,and increasing the concentration of BDNF can improve the PSD of rats.
Keywords/Search Tags:Post stroke depression, Xiao-yao-jie-yu-san, Fluoxetine capsule, BDNF, HAMD-17
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