Objective To explore the effects and related mechanisms of astragaloside Ⅳ on depression-like behavior in rats with post-stroke depression(PSD)induced by chronic unpredictable mild stress(CUMS).Methods Fifty-four healthy male Sprague Dawley rats were randomly divided into blank group,sham surgery group,physiological saline group,astragalosideⅣ group,fluoxetine group,and combination therapy group,with 9 rats in each group.Rats in the blank group were raised normally without any treatment.After anesthesia,rats in the sham surgery group were exposed to the common carotid artery through a longitudinal incision about 2 cm along the right neck.The incision was not processed and sutured directly,and the rest were the same as those in the blank group.Rats in the remaining four groups were first used to prepare rat stroke models according to the suture method,and then CUMS induction was performed to prepare PSD models.After successful modeling,the rats in the physiological saline group were given physiological saline(5 mL·kg-1)daily by gavage,the rats in the astragaloside Ⅳ group were given astragaloside Ⅳ suspension(25.0 mg·kg-1)daily by gavage,the rats in the fluoxetine group were given fluoxetine suspension(12.5 mg·kg-1)daily by gavage,and the rats in the combination therapy group were given astragaloside Ⅳ(25.0 mg·kg-1)and fluoxetine(12.5 mg·kg-1)suspensiondaily by gavage.All rats in the four groups were administered once a day for a total of 4 weeks.The rats in the blank group and sham surgery group did not undergo gastric lavage treatment.The body mass was measured once a week,and the sucrose preference test,open field test,and Morris water maze test were also conducted once a week until the end of the experiment.After the administration,the rats were euthanized.The expression levels of adenosine monophosphate-activated protein kinase(AMPK)and brain-derived neurotrophic factor(BDNF)mRNA in the hippocampus of rats in each group were detected by reverse transcription polymerase chain reaction.The relative content of AMPK and BDNF positive cells in the hippocampus of rats in each group was detected by immunohisto-chemical staining.The expression levels of AMPK and BDNF protein in the hippocampus of rats in each group were detected by Western blot.Results After 4 weeks of treatment,there was no statistically significant differences in body mass,sucrose preference rate,horizontal movement distance in open field test,and Morris water maze crossing frequency of rats between the blank group and the sham surgery group(P＞0.05);compared with the blank group and sham surgery group,the body mass,sucrose preference rate,horizontal movement distance in open field test,and Morris water maze crossing frequency of rats in the physiological saline group,astragaloside Ⅳ group,fluoxetine group,and combination therapy group were significantly reduced(P＜0.05);compared with the physiological saline group,the body mass,sucrose preference rate,horizontal movement distance in open field test,and Morris water maze crossing frequency of rats in the astragaloside Ⅳ group,fluoxetine group,and combination therapy group significantly increased(P＜0.05);there was no statistically significant differences in body mass,sucrose preference rate,horizontal movement distance in open field test,and Morris water maze crossing frequencyof rats among the astragaloside Ⅳ group,fluoxetine group,and combination therapy group(P＞0.05).After 4 weeks of treatment,there was no statistically significant differences in the relative content of positive cell,and the relative expressions of AMPK,BDNF mRNA and protein in the hippocampus of rats between the blank group and the sham surgery group(P＞0.05);compared with the blank group and sham surgery group,the relative content of positive cell,and the relative expressions of AMPK,BDNF mRNA and protein in the hippocampus of rats in the physiological saline group,astragaloside Ⅳ group,fluoxetine group,and combination therapy group significantly decreased(P＜0.05);compared with the physiological saline group,the relative content of positive cell,and the relative expressions of AMPK,BDNF mRNA and protein in the hippocampus of rats in the astragaloside Ⅳ group,fluoxetine group,and combination therapy group increased(P＜0.05);there was no statistically significant differences in the relative content of positive cell,and the relative expressions of AMPK,BDNF mRNA and protein in the hippocampus of rats among the astragaloside Ⅳ group,fluoxetine group,and combination therapy group(P＞0.05).Conclusion Astragaloside Ⅳ can improve depression-like behavior in CUMS-induced PSD rats,and its mechanism may be related to increasing the expression of AMPK and BDNF in the hippocampus.
Astragaloside Ⅳpost-stroke depressionadenosine monophosphate-activated protein kinasebrain-derived neurotrophic factor
维普
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