Dysregulation of endothelial cell specific molecule-1 expression during urosepsis-induced acute lung injury in rabbits

Abstract

Objective To explore the expression of endothelial cell specific molecule-1 (ESM-1) and inflammatory factors during urosepsis-induced acute lung injury (ALI) in rabbits, and the potential mechanism. Methods Urosepsis-induced ALI models in rabbits were assigned into three groups: control group, sham group and urosepsis group (0, 6, 12 and 36 h according to time points pre-scheduled). The rabbit urosepsis model was established by artificial high pressure in the infected pelvis. Lung histomorphological changes were observed by light microscope. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, ESM-1, lymphocyte function associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) in serum were analyzed by enzyme linked immunosorbent assay (ELISA). The expression of ESM-1, LFA-1 and ICAM-1 in serum was detected by ABC immunohistochemistry, and further the ESM-1/LFA-1 rate in lung tissue was calculated. Results As compared with the control group and sham group, urosepsis group had serious lung injury. The levels of serum TNF-α, IL-1β and IL-6 were elevated significantly in urosepsis group. After 6, 12, 24 and 36 h, the levels of TNF-α were (63.65±3.07), (128.17±4.26), (99.24±7.97), (49.36±6.09) ng/L; the levels of IL-1β were (232.77±21.54), (481.21±20.84), (220.23±22.21), (105.25±23.46) ng/L; the levels of IL-6 were (72.62±4.42), (122.51±6.77), (82.22±4.23), (60.05±2.82) ng/L. The expression levels in the urosepsis group were significantly higher than those in the control group and the sham group at each time point (After 36 h, TNF-α: F=96.932, P=0.000; IL-1β: F=9.001, P=0.007; IL-6: F=5.293, P=0.030). The expression of serum LFA-1 and ICAM-1 was increased over time in urosepsis group. After 6, 12, 24 and 36 h, the levels of LFA-1 were (12.50±5.71), (23.16±6.84), (45.04±7.65), (61.38±9.87) ng/L; the levels of ICAM-1 were (780.67±66.89), (1 034.16±72.33), (1 420.10±87.25), (1 834.23±88.46) ng/L, which were significantly different from those in the control group and the sham group (After 36 h, LFA-1: F=85.612, P=0.000; ICAM-1: F=456.901, P=0.000). Meantime, the levels of ESM-1 expression and ESM-1/LFA-1 rate in the lung tissue during urosepsis increased in the early stage of urosepsis but declined over time. The levels of LFA-1 were: 0.139±0.017, 0.274±0.024, 0.120±0.035, 0.089±0.031; the ESM-1/LFA-1 rate was: 1.188±0.019, 1.473±0.015, 0.529±0.020, 0.263±0.017, which were significantly different from those in the control group and the sham group (After 36 h, ESM-1: F=13.190, P=0.002; ESM-1/LFA-1: F=891.411, P=0.000). Conclusion The expression changes of ESM-1 may suggest the development process during urosepsis-induced ALI. The present study may offer beneficial reference for treating ALI, and decreasing multiple organs failure in earlier phase clinically. Key words: Endothelial cell specific molecule-1; Lymphocyte function associated antigen-1/Intercellular adllesion molecule-1; Urosepsis; Acute lung injury