Effect of Jieyu Formula on the expression levels of CB1R/CB2R and CRF in hippocampus of post-stroke depression rats
Objective:To explore the relevant biological mechanisms of Jieyu Formula(JYF)in treating post-stroke depression(PSD).Methods:60 healthy male SPF SD rats were randomly divided into sham-operated group,stroke group(MCAO group),post-stroke depression group(PSD group),JYF low-dose group,JYF high-dose group and fluoxetine group after behavioral scoring.The MCAO group was modeled by the middle cerebral artery occlusion(MCAO)method,and the PSD group,JYF low-dose group,JYF high-dose group and fluoxetine group were modeled by MCAO+chronic unpredictable mild stress(CUMS)method+solitary feeding method for post-stroke depression.Body mass and behavioral tests were performed at 0,3,5,and 7 weeks respectively.After 7 weeks,immunohistochemistry was used to detect the expression of cannabinoid type 1 receptor(CB1R)/cannabinoid type 2 receptor(CB2R)and corticotropin-releasing factor(CRF)in the hippocampus of rats in each group.Results:Body mass test results showed that before administration,compared with the sham-operated group,the body mass of the PSD group,JYF high-dose group,JYF low-dose group and fluoxetine group was significantly reduced(P<0.05);after administration,compared with the PSD group,the body mass of the JYF high-dose group and fluoxetine group was significantly increased(P<0.05).Forced swimming experiment results showed that before administration,compared with the sham-operated group,the immobility time of forced swimming in the PSD group,JYF high-dose group,JYF low-dose group and fluoxetine group was significantly increased(P<0.05)and the struggling time of forced swimming was significantly reduced(P<0.05);after administration,compared with the PSD group,the immobility time of forced swimming in the JYF low-dose group,JYF high-dose group and fluoxetine group was significantly reduced(P<0.05)and the struggling time of forced swimming was significantly increased(P<0.05).Sucrose preference test results showed that before administration,compared with the sham-operated group,the sucrose preference of the PSD group,JYF high-dose group,JYF low-dose group and fluoxetine group was significantly decreased(P<0.05);after administration,compared with the PSD group,the sucrose preference of the JYF low-dose group,JYF high-dose group and fluoxetine group was significantly increased(P<0.05).Immunohistochemistry results showed that compared with the sham-operated group,the expression of hippocampal CB1R and CB2R in hippocampal subfields(CA1,CA3 and DG)was significantly decreased in the PSD group(P<0.05),and the expression of hippocampal CRF in CA1,CA3 and DG regions was significantly increased in the PSD and MCAO groups(P<0.05).Compared with the PSD group,CB1R expression in CA1,CA3 and DG regions was significantly increased in the JYF low-dose group,JYF high-dose group and fluoxetine group(P<0.05),CB2R expression in CA1,CA3 and DG regions was significantly increased in the JYF high-dose group and fluoxetine group(P<0.05),CB2R expression in CA1 and DG regions was significantly increased in the JYF low-dose group(P<0.05),CRF expression in CA1,CA3 and DG regions was significantly decreased in the JYF low-dose group,JYF high-dose group and fluoxetine group(P<0.05).Conclusion:JYF can significantly improve the depression-like behavior and play a neuroprotective role in PSD rats,and its mechanism of action may be related to the up-regulation of CB1R and CB2R expression and the down-regulation of CRF expression in hippocampus.
NETL
NSTL
万方数据
