Objective:To explore the expression of connexin 43 (Cx43) in hippocampus of post-stroke depression (PSD) model rats and its effect on cell apoptosis and depressive-like behavior.Methods:Sixty SPF-grade male SD rats aged 6-8 weeks were randomly divided into five groups (12 rats in each group): normal group, stroke group, depression group, PSD group and carbenoxolone(CBX) group. The stroke model was established by injection of endothelin-1.Chronic unpredictable mild stress (CUMS) combined with solitary rearing was used to establish a depression model. Rats in PSD group were given CUMS and raised alone on the seventh day of stroke modeling.Rats in CBX group were given intraperitoneal injection of CBX(20 mg/kg) on 14th day after PSD modeling. The depressive-like behavior of rats was evaluated by sugar water preference test and open field test. The expression of Cx43 mRNA in hippocampus of rats was detected by RT-PCR, the expression levels of Cx43, caspase-3, Bax and Bcl-2 were detected by Western blot, and the changes of apoptosis rate were detected by TUNEL staining. SPSS 23.0 software was used for statistical analysis, the behavioral data were analyzed by repeated measurement ANOVA, the remaining data were analyzed by one-way ANOVA, and the LSD- t test was used for further pairwise comparison. Results:(1)As for the preference rate of sugar water and the times of crossing the grid, the interaction effects between time and group were significant among the 5 groups( Finteraction=35.57, 111.43, both P<0.05). On the 28th day after operation, the preference rate of sugar water and the times of crossing grid in depression group and PSD group were lower than those in stroke group (all P<0.05), while the preference rate of sugar water and the times of crossing grid in CBX group were both lower than those in PSD group (both P<0.05). (2) The levels of Cx43 mRNA and Cx43 protein in the five groups were significantly different ( F=273.57, 64.56, both P<0.05). The levels of Cx43 mRNA and Cx43 protein in depression group ((0.59±0.05), (0.69±0.08)) and PSD group ((0.61±0.07), (0.63±0.12)) were lower than those in stroke group ((1.01±0.03), (1.05±0.08)) (all P<0.05). The levels of Cx43 mRNA and Cx43 protein in CBX group ((0.30±0.01), (0.37±0.09)) were lower than those in PSD group (both P<0.05). (3) The protein levels of caspase-3, Bax, Bcl-2 and Bcl-2/Bax and the apoptosis rate of the five groups were significantly different ( F=102.40, 90.27, 47.42, 159.99, 115.21, all P<0.05). The levels of caspase-3, Bax protein, apoptosis rate in stroke group ((0.44±0.06), (0.54±0.07), (29.16±5.03)) and depression group ((0.45±0.07), (0.59±0.09), (27.00±4.93)) were higher than those in normal group ((0.21±0.08), (0.33±0.07), (4.83±3.18)) (all P<0.05), the levels of Bcl-2 protein and Bcl-2/Bax in stroke group ((0.80±0.04), (1.51±0.20)) and depression group ((0.60±0.09), (1.03±0.09)) were lower than those in normal group ((1.04±0.13), (3.14±0.38)) (all P<0.05).The levels of caspase-3, Bax protein and apoptosis rate in PSD group ((0.76±0.05), (0.84±0.02), (44.50±3.83)) were all higher than those in stroke group and depression group (all P<0.05), and the levels of Bcl-2 protein and Bcl-2/Bax in PSD group ((0.50±0.14), (0.59±0.17)) were lower than those in stroke group and depression group (both P<0.05). The levels of caspase-3 and Bax protein and the apoptosis rate in CBX group ((1.03±0.10), (1.02±0.05), (56.00±4.81)) were higher than those in PSD group (all P<0.05).The levels of Bcl-2 protein and Bcl-2/Bax in CBX group((0.26±0.08), (0.25±0.08)) were lower than those in PSD group (both P<0.05). Conclusion:The expression level of Cx43 in the hippocampus of PSD model rats is downregulated, which can promote cell apoptosis and exacerbate depressive behavior.