Abstract：Objective To study the effect of early intervention with lipoxin A4 (LXA4) on septic mice. Methods Healthy male Balb/c mice aged 6-8 weeks were randomly divided into sham-operation group, sepsis group, 1-hour intervention group (intervention at 1 hour after sepsis), and 6-hour intervention group (intervention at 6 hours after sepsis) (n=8 each). A sepsis model was prepared by cecal ligation and puncture. The intervention groups received LXA4 at 0.01 μg/g body weight 1 or 6 hours after the model was established. Blood was taken from eyeballs at 24 hours after operation. Peritoneal lavage fluid and liver and lung tissue samples were collected. The bacterial colonies of whole blood and peritoneal lavage fluid were counted by dilution plating. The serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) were determined by cytometric bead array. The serum level of high mobility group box-1 (HGMB1) was determined using ELISA. The percentages of macrophages and neutrophils in peritoneal lavage fluid were determined by flow cytometry. Paraffin sectioning and hematoxylin-eosin staining were performed for the liver and lung tissue samples to observe pathological damage. Results Compared with the sham-operation group, the sepsis group had a significantly decreased percentage of macrophages and a significantly increased percentage of neutrophils in peritoneal lavage fluid (P < 0.05), as well as significantly increased serum levels of IL-6, TNF-α, MCP-1, and HMGB1 (P < 0.05); in addition, the sepsis group showed more vacuolar degeneration, hepatocyte swelling, and inflammatory cell infiltration in liver tissue, and more capillary congestion, pulmonary septal thickening, inflammatory cell infiltration, and partial tissue destruction in lung tissue. Compared with the sepsis group, the 1-hour and 6-hour intervention groups had a significantly increased percentage of macrophages in peritoneal lavage fluid (P < 0.05) and significantly reduced bacterial load in whole blood (P < 0.05), serum levels of IL-6, TNF-α, MCP-1, and HMGB1 (P < 0.05), and degree of liver and lung tissue damage and inflammatory cell infiltration, but there was no significant difference in the percentage of neutrophils and bacterial load in peritoneal lavage fluid (P > 0.05). Compared with the 6-hour intervention group, the 1-hour intervention group had a significantly decreased serum level of HMGB1 (P < 0.05), but there was no significant difference in other indicators between the two groups (P > 0.05). Conclusions Early intervention with LXA4 may attenuate liver and lung injuries in septic mice, which may be explained by the decrease in serum levels of IL-6, TNF-α, MCP-1, and HMGB1, and it also may reduce the bacterial dissemination in the whole blood of septic mice, which may be explained by the increase in the percentage of peritoneal macrophages.
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