| Depression is a kind of affective disorder,with the clinical feature of negative,pessimistic,inattention,lose interest in things,sleep and eating disorders and so on.The pathogenesis of depression is complex,while,most of patients show symptoms in molecular biology as hypofunction or insufficient of monoamine neurotransmitter,dysfunction of hypothalamic-pituitary-adrenal,impairment of neurotrophic factors and inflammatory reaction.Based on these symptoms,most of the drugs used for the treatment of depression are chemical agents such as the neurotransmitter reuptake inhibitors,5-HT receptor inhibitor and so on.Therefore,it is significant to explore a effective and harmfulless medicine for the treatment of depression.Baijin capsule which showed well therapeutic effect on depression was originally derived from formula of clinical experence.However,the pharmacodynamics study on Baijin capsule have not been carried out,and the pathogenesis of depression of Baijin capsule is ambiguous.Thus,in order to verify the antidepressant-like activity and clarify the antidepressant mechanism,studies on the rat depression model caused by chronic unpredictable mild stress and the rat depression model caused by olfactory bulbectomy were carried out from the perspective of monoamine neurotransmitter,HPAA and proinflammatory cytokine.1 Effect of Baijin capsule on rat depression model caused by chronic unpredictable mild stressObjective:Investigate the anti-depression effect of Baijin capsule on depressed rat,and clarify the antidepressant mechanism.Methods:96 SD rats,selected from 112 rats according to their comprehensive score of body weight,sugar water experiment and open field test,were divided into 6 groups:control group,model group,fluoxetine group,Baijin capsule group with high dosage,middle dosage,and low dosage.Body weight,sweet water wastage and open field test were used to evaluate the established depression model after being given chronic unpredictable mild stress for 7 weeks continuously.Then give corresponding medicines by oral administration for 4 weeks continuously,after establishing the model successfully.And body weight,autonomic activity times,sweet water wastage and open field test were detected to evaluate the anti-depression effect of Baijin capsule.After then,monoamine neurotransmitter in the cerebral cortex,and hippocampus of the rats were determined by HPLC,and CORT,ACTH,CRH and proinflammatory factor in the serum of the test rats were determined by radioimmunoassay to explore the possible the antidepressant mechanism of Baijin capsule.Results:Compared with the rat in control group,the body weight,autonomic activity times,sweet water wastage,horizontal movement distance and the number of vertical movement of the rat were all decreased obviously(P<0.01).Compared with the model rat,autonomic activity times of the rat in middle and low dose group of Baijin capsule were increased(P<0.05);sweet water wastage,horizontal movement distance and the number of vertical movement of the rat in Baijin capsule group were all increased(P<0.05,P<0.01),which mean that Baijin capsule possess anti-depression effect on the depression rat.Compared with the control group,the concentrate of DA,DOPAC,NE,and 5-HT in the cerebral cortex in model rat had the tendency to reduce.While metabolic rates of(DOPAC+HVA)/DA,and 5-HIAA/5-HT in the cerebral cortex were elevated(P<0.05).The concentrateions of 5-HT,5-HIAA,and HVA in hippocampus of the model rat were decreased(P<0.05,P<0.01),and the metabolic rate of 5-HIAA/5-HT in the hippocampus was increased(P<0.05).The CRH,TNF-α,IL-6 in the serum were changed drastically(P<0.05).However,compared with the model,Baijin capsule could inhibit the change of the monoamine neurotransmitter,CRH,TNF-α and IL-6 of the rat in the model group(P<0.05,P<0.01).Conclusion:Baijin capsule possess the effect of anti-depression,and the anti-depression effect might be related to the regulation effect of Baijin capsule on the content of monoamine neurotransmitter in the cerebral cortex and on the content of CRH,TNF-α and IL-6 in the rat plasma.2 Effect of Baijin capsule on rat depression model caused by olfactory bulbectomyObjective:Investigate the anti-depression effect of Baijin capsule on depressed rat,and clarify the antidepressant mechanism.Methods:96 SD rats were divided into sham-operated group(16)and operating group(80).Then the olfactory bulb of the rat in the operating group were destroyed,and penicillin was used for avoiding infection.After establishing the model successfully,the 80 rats in the operating group were divided into 5 groups:model group,fluoxetine group,Baijin capsule group with high dosage,middle dosage,and low dosage.The body weight and autonomic activity times were determined to evaluate the established model.And then the body weight,autonomic activity times,novelty-suppressed feeding,and open field test were carried out to investigate the anti-depression effect of Baijin capsule,after giving corresponding medicines by oral administration for 4 weeks continuously.In order to study on the anti-depression mechanism of Baijin capsule,the neurotransmitter in the cerebral cortex of the rat in the Baijin capsule group were determined by LC-MS/MS,and the the CORT,ACTH,CRH and proinflammatory factor were determined by radioimmunoassay.At the same time,Real-time PCR were used to determine the expression of 5-HT1A/2A and mGlu receptors.Results:Compared with the rat in the control group,autonomic activity times,horizontal movement distance,and the number of vertical motion of the rat in the model rat were increased(P<0.05,P<0.01).Feeding latency in the model rat was evidently extended(P<0.01).Compared with the rat in the model group,autonomic activity times,horizontal movement distance,and the number of vertical motion of the rat in the Baijin capsule group were decreased dramatically(P<0.05).Compared with the rat in the control group,the content of 5-HT,DA and Orn in cerebral cortex were decreased apparently(P<0.05),the expression of 5-HT1A receptor was also down-regulate(P<0.01);the content of 5-HIAA,DOPAC,HVA,Glu,and ASP were increased obviously(P<0.05),and the value of(DOPAC+HVA)/DA was also increased distinctly(P<0.05).The content of CORT,TNF-α,IL-6 and IL-1β in rat plasma were increased(P<0.05).The expression of 5-HT2A and mGlu receptors were up-regulate(P<0.05).Compared with the rat in the model group,the the content of 5-HT,DA and Orn and the expression of 5-HT1AR in cerebral cortex of the rat in the Baijin capsule group were increased dramatically,while the content of Glu,and ASP and the expression of 5-HT2AR were decreased,and the value of(DOPAC+HVA)/DA and 5-HIAA/5-HT were decreased(P<0.05,P<0.01).The content of CORT,TNF-α and IL-6 in rat plasma were decreased(P<0.05,P<0.01).Conclusion:Baijin capsule possess the effect of anti-depression,and the anti-depression effect might be related to the regulation effect of Baijin capsule on the content of monoamine neurotransmitter and its receptors,Amino acid in the cerebral cortex and on the content of CRH,TNF-α and IL-6 in the rat plasma.Summary1 This study adopts the depression rat model with chronic unpredictable mild stress or the model of olfactory bulb.These two kinds of animal models has been successfully showed the loss of sensation,autonomic activity change,and the change of the detection desire of the outside world fresh environment and feeding,which could show that models had been established successfully.2 Baijin capsule can alleviate depression animal model which showed a lack of pleasure,autonomous activity change,the change of the ability to explore new environment and feeding capacity,which can show the antidepressant effect of Baijin capsule.3 The antidepressant mechanism of Baijin capsule may be related to regulating the content of monoamines neurotransmitter,and amino acid and regulating its receptor expression in the cerebral cortex,regulation and control function of HPA axis and promoting inflammatory cytokine levels in the serum. |
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