Neutrophil elastase in dexmedetomidine alleviating sepsis-related renal injury in rats

Abstract

Background: This research was to investigate the mechanism of neutrophil elastase (NE) in dexmedetomidine (DEX) alleviates sepsis-related renal injury in rats.

Methods: Sixty healthy male SD rats aged 6-7 weeks were randomly assigned to the control group (Sham group (S group)), Model group (M group), Model + DEX group (M + DEX group), and Model + DEX + Elaspol group (M + DEX + Elaspol (sivelestat) group), with 15 rats in each group. The renal morphology and pathological changes of different groups of rats after modeling were observed, and renal tubular injury was scored. Serum samples were collected at 6 h, 12 h, and 24 h after modeling, and the rats were sacrificed. Renal function indicators, including neutrophil gelatinase-associated lipoprotein (NGAL), kidney injury molecule-1 (KIM-1), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), NE, serum creatinine (SCr), and blood urea nitrogen (BUN), were analyzed by enzyme-linked immunosorbent assay at different time periods. The level of NF-кB in renal tissue was detected by immunohistochemistry.

Results: It was revealed that the general color of renal tissue in M group was dark red, swollen, and congested, and the renal tubular epithelial cells were significantly enlarged, with obvious vacuolar degeneration and inflammatory cell infiltration. Compared with M group, the color and morphology of renal tissue in M + DEX group and M + DEX + Elaspol group were improved, and the amount of inflammatory cell infiltration was reduced. The renal tubular injury score, SCr level, BUN level, NGAL level, KIM-1 level, TNF-α, IL-6, NE level, and NF-кB level in M group were significant different from S group 12 h after the operation (P < 0.001). The renal tubular injury score, SCr level, BUN level, NGAL level, KIM-1 level, TNF-α, IL-6, NE level, and NF-кB level in M + DEX group were significant different from M group (P < 0.01). The renal tubular injury score, SCr level, BUN level, NGAL level, KIM-1 level, TNF-α, IL-6, NE level, and NF-кB level in M + DEX + Elaspol group were significant different from those in M group at 12 h after the operation (P < 0.001).

Conclusion: NE plays an active role in the reduction of sepsis-related renal injury in rats by inhibiting the inflammatory response.

Keywords: Inflammatory response; Neutrophil elastase; Rats; Renal injury; Sepsis.