Objective Explore the mechanism of C-X-C chemokine receptor 4 (CXCR4) on the apoptosis of lymphocytes in a lipopolysaccharide (LPS) induced sepsis model mice.Methods 18 male C57 mice were randomly divided into Control group, LPS group, and LPS + Plerixafor group. The Control group was injected with saline, the LPS group was injected with LPS, and the LPS + Plerixafor group was subcutaneously injected with Plerixafor one hour after LPS injection. Clinical symptom scoring was performed two hours after modeling, and blood, spleen, and thymus samples were collected one hour after scoring. The spleen and thymus were used for HE staining and Western blot analysis to detect the expression of CXCR4, Cyclin B1, Mitotic Arrest Deficient 2-Like 1 (Mad2L1), Securin, Cdc20, and Budding Uninhibited by Benzimidazoles 1-Related 1 (BubR1) proteins. ELISA was used to detect serum levels of Tumor Necrosis Factor-alpha (TNF-α), Interleukin-6 (IL-6), and Interleukin-1 beta (IL-1β), and flow cytometry was used to detect peripheral blood lymphocyte apoptosis.Results ① Compared with the Control group, mice in the LPS group exhibited lethargy, reduced activity, increased respiratory rate, increased heart rate, secretion in the eyes and nasal cavity, and even symptoms such as fever, abdominal distension, and piloerection, with significantly increased MSS scores (P<0.0001). The expression of TNF-α, IL-6, IL-1β, CXCR4, Mad2L1, Cdc20, and the proportion of lymphocyte apoptosis were significantly upregulated, while CyclinB1, Securin, and BubR1 expressions were significantly downregulated, with significant differences between groups (P<0.001). The spleen tissue structure was disordered, structural density decreased, the number of lymphocytes in the spleen tissue decreased, the thymus tissue structure was disordered, the number of lymphocytes decreased, and structural density decreased; ② Compared with the LPS group, the above manifestations in the LPS+Plerixafor group were significantly alleviated, with decreased MSS scores (P<0.0001), downregulated expression of TNF-α, IL-6, IL-1β, CXCR4, Mad2L1, Cdc20, and the proportion of lymphocyte apoptosis, with significant differences between groups (P<0.01). The expression of CyclinB1, Securin, and BubR1 was upregulated, with significant differences between groups (P<0.01). The number of lymphocytes in the spleen tissue increased, structural density improved, and the number of lymphocytes in the thymus tissue increased, with better structural density. ③ Correlation analysis revealed that CXCR4 expression was positively correlated with TNF-α, IL-6, IL-1β, Mad2L1, Cdc20 expression, and the proportion of lymphocyte apoptosis (R values were 0.9100, 0.9465, 0.9875, 0.9551, 0.9824, 0.9845, P<0.01); CXCR4 expression was negatively correlated with CyclinB1, Securin, and BubR1 expression (R values were 0.9155, 0.8471, 0.7579, P<0.01); Mad2L1 and Cdc20 expression were positively correlated with the proportion of lymphocyte apoptosis (R values were 0.9857, 0.9610, P<0.0001); CyclinB1, Securin, and BubR1 expression were negatively correlated with the proportion of lymphocyte apoptosis (R values were 0.8643, 0.7830, 0.6755, P<0.01). Conclusions CXCR4 can influence cell mitotic slippage by regulating the SAC-MCC-APC/C pathway, mediating lymphocyte apoptosis, and its inhibitor Plerixafor can suppressed lymphocyte apoptosis, thereby improving the prognosis of septic mice.

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