Effect of Xingnao Jieyu recipe on behavior of rats with post-stroke depression and its mechanism

YUN Yedong; YANG Yifan; YIN Jun; HU Zhouyuan; MAO Meiling; YAN Yongmei

doi:10.3969/j.issn.1002-266X.2024.34.002

Abstract：Objective To investigate the effect of Xingnao Jieyu recipe(XNJY)on behavior of rats with post-stroke depression(PSD)and the mechanism of action.Methods Seventy-two male SD rats were randomly divided into six groups:control(Con),stroke(MCAO),PSD,low-dose XNJY(XNJY-L),high-dose XNJY(XNJY-H),and fluoxetine(Flu)groups.We established the stroke models using the MCAO method in all groups except the Con group.Neurological function was evaluated using the Longa 5-point scale,and we included only rats scoring 1-3 in subsequent experiments.We created PSD models in all groups except Con and MCAO by subjecting the rats to 21 days of chronic unpredictable mild stress(CUMS).Drug interventions began on the second day after stroke modeling and continued for 21 days.We assessed body weight,behavior,and hippocampal pathology through HE staining.Serum IL-6 and IL-10 levels were measured us-ing ELISA,and Western blotting was employed to detect the expression levels of hippocampal Keap1,nuclear factor E2-as-sociated factor 2(Nrf2),and heme oxygenase(HO-1)protein.Results Compared with the Con group,the PSD group had lower body weight,shorter forced swimming time,lower sucrose consumption,and lower scores of horizontal and verti-cal movements(all P<0.05);in the PSD group,the number of neurons in the hippocampal tissues decreased and became sparse,the intercellular space widened,the cell bodies shrank and dissolved,and the cytoplasm and cell nuclei even be-came hollow and disappeared;Keap1 protein expression was up-regulated,while Nrf2 and HO-1 levels decreased,and se-rum IL-6 and IL-10 levels decreased(all P<0.05).Compared with the PSD group,the XNJY-L,XNJY-H,and Flu groups had higher body weight,longer forced swimming time,higher sucrose consumption,and higher scores of horizontal and vertical movements(all P<0.05).The structure of nerve cells in the hippocampal tissues remained mostly intact with a relatively minor degree of damage;the cells were closely arranged,and there was an abundance of Nissl bodies;the structures such as cell nuclei and cytoplasm remained intact;the protein expression levels of Nrf2 and HO-1 in the hippo-campus were up-regulated and the levels of IL-6 and IL-10 in the serum increased(all P<0.05).Conclusions Xingnao Jieyu recipe improves depressive-like behavioral symptoms in PSD rats,exerting an anti-depressant effect to achieve the treatment goal for PSD.Its mechanism may be related to the inhibition of oxidative stress in hippocampal neural tissues,activation of the Nrf2/HO-1 signaling pathway,and enhancement of antioxidant capacity.