Abstract:Objective To construct an animal model of post-stroke depression (PSD) based on the theory of “depression, stasis, phlegm” , with a focus on the development and validation of an objective assessment system. Methods Rats were randomly divided into five groups: control group, depression group, stroke group, PSD group, and Baishile decoction group. A PSD syndrome-based animal model was established using a combination of middle cerebral artery occlusion (MCAO) and chronic unpredictable mild stress (CUMS). After model establishment, the “depression, stasis,phlegm” were evaluated using morris water maze, open field test,forced swim test,sucrose preference test, neurotransmitter levels, brain tissue pathology, tongue and claw color RGB values, and blood rheology. Results PSD rats exhibited significant reductions in target quadrant dwell time, platform crossings, climbing, and rearing frequencies, a significant decrease in the percentage of sucrose preference, and a significant increase in immobility time in the forced swim test. HE and Nissl staining revealed significant brain tissue damage in PSD rats. Serum and cerebrospinal fluid levels of 5-HT were significantly decreased, while Glu levels were significantly increased. Tongue and claw color RGB values were all decreased. Blood rheology showed a hypercoagulable state. Blood lipid metabolism-related indicators were significantly abnormal. The Baishile decoction group showed significant improvements compared to the PSD group, including increased target quadrant dwell time, the number of platform crossings, the times of climbing, rearing frequencies, and the percentage of sucrose preference,decreased immobility time in the forced swim test, improved brain tissue pathology, increased serum and cerebrospinal fluid levels of 5-HT, decreased Glu levels, increased tongue and claw RGB values, and varying degrees of improvement in blood rheology and blood lipid metabolism-related indicators. Conclusion The combination of MCAO and CUMS successfully constructed a syndrome-based animal model that exhibits the characteristics of “depression, stasis, phlegm”, and established corresponding objective assessment criteria.