Uti Journal Of Endotoxin-induced Acute Renal Injury In Rats

Objective To explore the role of Ulinastatin (UTI) in lipopolysaccharide (LPS)-induced acute kidney injury (AKI) in rats.Methods Thirty male Wistar rats were randomly divided into three groups: control group, LPS group and LPS+UTI group. The rats were injected with normal sodium 1ml via caudal vein in control group, with LPS 5 mg/kg via caudal vein to establish AKI model in LPS group, with UTI 105 U/kg after injection with LPS in LPS+UTI group. Six hours later, the following examinations were carried out: the blood and urine levels of Interleukin-18 (IL-18) were determined with Enzyme-linked immunosorbent assay (ELISA). Immunohistochemistry was used to determine the concentration of nuclear factor-κB (NF–κB) in kidney tissue in rats. The creatinine clearance rates (Ccr) were measured and the morphological changes of kidney were observed under light microscope and electron microscope.Results Compared with those in control group and LPS+UTI group, Ccr significantly decreased in LPS group (P<0.01), but there was no significant difference between LPS group and LPS+UTI group (P>0.05). The levels of blood and urine IL-18 were elevated in LPS group compared with normal controls and LPS+UTI group (P<0.01). The concentration of NF–κB in LPS group was significantly higher than in control group and LPS+UTI group, (P<0.01).The level of NF–κB in LPS+UTI group was also little higher than in control group (P<0.05). Pathological section and microscope section also showed that the inflammation reaction of kidney in LPS+UTI group was lighter than in LPS group. Under the electron microscope, the renal tubule epithelium in normal rats showed large and round-shaped nuclei, intact brush border and mitochondria, whereas pyknosis, rupture of mitochondrial cristae, vacuolization and disrupted microvilla were found for the LPS group in contrast to the nearly normal morphology in the LPS+UTI group expected for sparsely identifiable resolution of mitochondrial cristae.Conclusion UTI may reduce the expression of pro-inflammatory IL-18 and NF–κB, hence its protection against LPS-induced AKI in rats.