To study the effect of ulinastatin (UTI) on acute kidney injury (AKI) in septic rats and explore the possible mechanism involved.

Thirty-two SD rats were randomly divided into four groups: blank control group, lipopolysaccharide group (LPS group), ulinastatin treatment group (LPS+UTI group), and p38 MAPK blocker intervention group (LPS+SB group). A rat model of sepsis was induced by LPS. The expression of TNF-α and TGF-β1 in renal tissues was detected by ELISA, and the expression of phosphorylated p38 MAPK protein in renal tissues was detected by Western blot. The pathomorphological changes of glomeruli and renal tubules were observed by light microscopy and electron microscopy.

Compared with the blank control group, the LPS group showed glomerular hyperemia and swelling, renal balloon dilation, obvious swelling of proximal convoluted renal tubule epithelial cells, weak nuclear staining, partial nuclear concentration, breakage, and even dissolution, renal interstitial hyperemia, edema, and a large amount of inflammatory cell infiltration. Electron microscopy showed that the endothelial cells of glomerular capillaries disappeared or were occluded, the basement membrane partially fractured and disappeared, the foot processes of podiocytes extensively fused and disappeared, and the mitochondria in the epithelial cytoplasm of proximal convoluted renal tubules were disorganized, with a fuzzy structure, marked swelling, and vacuolated phenomenon. The expression of TNF-α, TGF-β1, and p38 MAPK proteins in renal tissues increased significantly. Compared with the LPS group, the expression of TNF-α, TGF-β1, and p38 MAPK proteins in the LPS+UTI group was decreased compared with the LPS group [TNF-α (pg/ml): 4915.00±267.06 vs 8836.00±739.51; TGF-β1 (pg/ml): 257.71±23.88 vs 354.39±29.44; P-p38 MAPK/β-actin: 0.158±0.022 vs 0.300±0.044, P＜0.05]. The expression of TNF-α, TGF-β1, and p38 MAPK proteins in the LPS+SB group was decreased compared with the LPS group [TNF-α (pg/ml): 4856.75±167.23 vs 8836.00±739.51; TGF-β1 (pg/ml): 249.56±23.42 vs 354.39±29.44; P-p38 MAPK/β-actin: 0.136±0.017 vs 0.300±0.044, P＜0.05], but there was no significant difference between the LPS+UTI group and LPS+SB group (P＞0.05).

Ulinastatin protects against septic acute kidney injury possibly by inhibiting the TGF-β1/p38 MAPK signal transduction pathway.