Therapeutic effect of Xingnao Jieyu decoction on post-stroke depression in rats and its mechanism
Objective To observe the therapeutic effect of Xingnao Jieyu decoction on post-stroke depression(PSD)in rats and to investigate the relationship between its mechanism and hypothalamus-pituitary-adrenal(HPA)axis in PSD rats.Methods Sixty male SD rats were randomly divided into the normal control group,PSD group,fluoxetine group,low-dose Xingnao Jieyu decoction group,and high-dose Xingnao Jieyu decoction group,with 12 rats in each group.The rats in the normal control group were fed normally without intervention,and rats in the other four groups were subjected to middle cerebral artery occlusion and chronic unpredictable mild stimulation(CUMS)to establish the PSD models.During CUMS,rats in the fluoxetine group were given fluoxetine solution of 0.2 mg/100 g,rats in the low-dose Xingnao Jieyu de-coction group and high-dose Xingnao Jieyu decoction group were given 1.05 and 2.10 g/mL Xingnao Jieyu decoction by gavage,and rats in the normal control group and PSD group were given 1 mL/100 g normal saline.Depression was as-sessed by body weight,forced swimming test,sucrose consumption test and open field test.The rats were sacrificed,and the brain tissues were removed.The pathological changes of hippocampus were observed by HE staining.The serum levels of HPA axis-related adrenocorticotropic hormone(ACTH)and cortisol(CORT)were detected by ELISA.Western blotting was used to detect the expression levels of glucocorticoid receptor(GR)in hippocampus and corticotropin-releasing hor-mone(CRH)in hypothalamus.Results Compared with the normal control group,the PSD group had lower body weight,shorter forced swimming test time,less sugar consumption,and lower horizontal and vertical movement scores,smaller number of neurons in the hippocampus of rats which showed inflammatory changes,higher levels of ACTH and CORT in serum,lower expression of GR protein in hippocampus of rats,and higher expression level of CRH protein in hy-pothalamus(all P<0.01).Compared with the PSD group,body weight,forced swimming time,sugar consumption,hori-zontal and vertical movement scores increased,most of the hippocampal cell structure remained intact,the degree of dam-age was lighter,the edema phenomenon was reduced,the cell survival rate increased,and the cells were closely arranged,the levels of ACTH and CORT in serum decreased,the expression of GR protein in hippocampus was up-regulated,and the expression of CRH protein in hypothalamus was down-regulated in the fluoxetine group,the low-dose and high-dose Xingnao Jieyu decoction groups(all P<0.01).Conclusion Xingnao Jieyu decoction can improve the depression-like be-havior of PSD rats;the mechanism may be that it inhibits the excessive activation of HPA axis and thus alleviate the dam-age of hippocampal neurons.
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