| Objective : By establishing a rat model of post-stroke depression,the effects of Xingnaojieyu recipe on body weight,behavior,hippocampal neuron morphology,serum levels of adrenocorticotrophic hormone and corticosterone,hippocampal glucocorticoid receptor and hypothalamic corticosteroid releasing hormone protein expression in PSD model rats were observed.To explore whether Xingnaojieyu recipe can inhibit HPA axis hyperfunction by regulating hypothalamic-pituitary-adrenal axis related hormones,so as to provide certain experimental basis for clarifying the neuroendocrine mechanism of PSD.Methods:A total of 72 healthy adult male SD rats were divided into 6 groups(12 rats in each group): blank group,stroke group,model(PSD)group,fluoxetine group,and Xingnaojieyu recipe(low and high dose groups),each group was fed for 7 days.The rats in each group were scored for neurological deficits within 24 hours after cerebral ischaemia-reperfusion;and the interventions were performed at the same time as CUMS stimulation.The rats were given fluoxetine solution once a day for 21 days.Changes in body weight and behaviour(forced swimming,sugar water consumption,open box test)of the rats were observed and recorded during the experiment.Changes in body weight and behaviour(forced swimming,sugar water consumption,open box test)were observed and recorded during the experiment.After the 21 st day of intervention,each group of rats was blood collected from the abdominal aorta and perfused into the brain,and HE staining was performed to observe the histomorphological changes in the rat hippocampus;ELISA was used to detect the serum ACTH and CORT levels;Western blot was used to detect the expression levels of GR and hypothalamic CRH protein in the rat hippocampus.Results:1.Effects of Xingnaojieyu recipe on body weight and behavior of rats: At the 11 th day of the experiment,compared with the blank group,the PSD group showed significantly lower body weight,shorter forced swimming time,significantly lower sugar water consumption,and significantly lower horizontal and vertical exercise scores,all of which were significantly different(p<0.01).Compared with the PSD group,there were statistically significant differences in the changes in body weight,swimming time and horizontal exercise score in the fluoxetine group,the low-dose group and the high-dose group of Awakening and Depression Relief Formula(p<0.05),but there were no statistically significant changes in the vertical exercise score in the low-dose group and the high-dose group of Awakening and Depression Relief Formula and the changes in sugar and water consumption in the low-dose group(p>0.05).At the 21 st day of the experiment,compared with the blank group,the PSD group had significantly lower body weight,shorter forced swimming time,significantly lower sugar and water consumption,and significantly lower horizontal and vertical exercise scores,all of which were significantly different(p<0.01).Compared with the PSD group,there were statistically significant changes in body weight,swimming time,horizontal and vertical exercise scores in the fluoxetine group,the low-dose group and the high-dose group(p<0.05),especially a significant increase in sugar water consumption in the fluoxetine group and the low-dose group,but no statistically significant change in sugar water consumption in the high-dose group(p>0.05).2.The effect of Xingnaojieyu recipe on the histopathological morphology of hippocampal tissue of rats in PSD model: The neurons in the hippocampal tissue of the rats in the stroke and PSD groups were obviously missing in number,loosely arranged,with blurred outline,swollen cytosol and disappeared nucleus,showing inflammatory changes;the neurons in the hippocampal tissue of the rats in the fluoxetine group and the rats in each dose group were basically intact,with less damage,less edema,more cell survival and more dense arrangement than those in the PSD group.3.Serum ACTH and CORT levels in rats: compared with the blank group,the serum ACTH and CORT levels in the PSD and stroke groups increased significantly(p<0.01);compared with the PSD group,the serum ACTH levels in the fluoxetine group and the low-dose group of Xingnaojieyu recipe decreased(p<0.05),and the ACTH levels in the low-dose group of Xingnaojieyu recipe decreased more significantly(p<0.01).However,the expression of serum ACTH in the rats in the high-dose group was slightly reduced compared with that in the PSD group,but the difference was not statistically significant(p>0.05).Compared with the PSD group,the serum CORT levels of rats in the fluoxetine group and the low and high dose groups of Xingnaojieyu recipe were all reduced(p<0.05),among which the serum CORT levels of rats in the fluoxetine group and the low dose group of Xingnaojieyu recipe were particularly reduced(p<0.01).4.Rat hippocampal GR and hypothalamic CRH protein expression levels: compared with the blank group,the hippocampal GR protein expression levels were significantly lower in the PSD and stroke groups(p<0.01);compared with the PSD group,the hippocampal GR protein expression levels were significantly up-regulated in the fluoxetine group and the low and high dose groups of Xingnaojieyu recipe(p<0.01);compared with the blank group,the hypothalamic CRH protein expression levels were significantly higher in the PSD and stroke groups(p<0.01).Compared with the blank group,the expression levels of CRH protein in the hypothalamus of rats in the PSD and stroke groups were increased(p<0.01),and compared with the PSD group,the expression levels of CRH protein in the hypothalamus of rats in the fluoxetine group and each dose group of Xingnaojieyu recipe were significantly down-regulated(p<0.01).Conclusion:1.Xingnaojieyu recipe has antidepressant effects on PSD model rats,and can significantly improve depression-like behaviours of lack of pleasure,loss of interest,despair state and reduced activity in PSD rats.2.Xingnaojieyu recipe can reduce hippocampal neuronal damage and improve the degree of histopathological changes in PSD model rats.3.Xingnaojieyu recipe can regulate HPA axis dysfunction and inhibit HPA axis hyperfunction by lowering serum levels of ACTH and CORT,as well as up-regulating hippocampal GR protein expression levels and lowering hypothalamic CRH protein expression levels,thus effectively exerting the effect of treating PSD. |
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