Objective To investigate the mechanism of the high mobility group box protein 1 (HMGB1) inhibitor on T lymphocytes and monocytes in sepsis. Methods Thirty C57BL/6 male mice were randomly divided into 3 groups, 10 in each group, followed by a sham operation group, a model group, and an inhibitor group. In the model group and inhibitor group, a mouse model of sepsis was replicated by cecal ligation and puncture (CLP). In the sham operation group, the wound was sutured only after exposure to the cecum, and no ligation was performed. The mice in the inhibitor group were intraperitoneally injected with glycyrrhizic acid, a specific inhibitor of HMGB1 (10 mg/kg), and injected once every 6 hours for 4 times. The mice in the sham operation group and the model group were intraperitoneally injected with the same amount of normal saline. After the mice were sacrificed, the thymus tissue of the mice was aseptically isolated, and the T lymphocytes and monocytes in the thymus were routinely extracted. MTT assay and flow cytometry were used to detect the proliferation activity and apoptosis of T lymphocyte. Transwell chemotaxis assay and ELISIA method were used to detect the chemotactic activity of monocytes and the expression levels of TNF-α, IL-6 and IL-10. Western blot was used to detect the expression levels of HMGB1 and phosphatase and tensin homolog deleted onchromosometen (PTEN) in each group. Results Compared with the sham operation group, the proliferation activity and the apoptosis rate of T lymphocytes in the thymus tissue of the model group, the chemotactic activity of monocytes and the expression levels of TNF-α, IL-6, IL-10 and the expression of HMGB1 and PTEN significantly increased (all P<0.05). Compared with the model group, the apoptosis rate of T lymphocytes, the expression levels of TNF-α, IL-6, HMGB1 and PTEN significantly reduced in inhibitor group mice, the proliferation activity of T lymphocytes, the chemotactic activity of monocytes, and the expression of IL-10 protein significantly increased (all P<0.05). Conclusions HMGB1 inhibitor can reduce the apoptosis rate of thymic T cells in septic mice, enhance the proliferation activity of T cells and the chemotactic activity of monocytes, increase the secretion of monocyte anti-inflammatory factor IL-10, and inhibit the pro-inflammatory factor TNF -α, IL-6 secretion.
Key words
High mobility group protein B1; /
Phosphatase and tensin homolog deleted onchromosometen; /
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Sepsis; /
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T lymphocyte; /
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Monocyte; /
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Mouse
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