To establish an animal model of urogenic sepsis and simulating acute kidney injury (AKI) caused by acute ureteral obstruction and infection. To explore the mechanism of action of glycyrrhizic acid (GA) on acute kidney injury related to urinary sepsis.

Twenty male healthy New Zealand rabbits were divided into four groups with five rabbits in each group: control group, sham operation group, sepsis group, sepsis + glycyrrhizin group. Control group did not receive any treatment, only with free diet. In the sham operation group, the left upper middle segment of the ureter was exposed, and no other treatment was done. In the sepsis group, E. coli (ATCC 25922) at a concentration of 10⁸ cfu/mLwas injected into the left ureter of rabbits at the rate of 0.5 mL/kg, and then the distal end of the ureter was ligated with silk suture to replicate the model of urogenic sepsis caused by acute ureteral obstruction and infection. In sepsis + glycyrrhizic acid group, on the basis of sepsis group, glycyrrhizic acid solution of 5 mg/kg was injected through ear vein for 3 consecutive days. At 72 h after operation, peripheral blood white blood cell count, neutrophil count, C-reactive protein, serum creatinine and urea nitrogen were detected. The contents of high mobility group box 1 (HMGB1), TNF-α, IL-1β and IL-6 in serum were determined by ELISA. Renal tissue of each group was stained with HE to evaluate inflammatory infiltration and renal tubular injury. The expression of HMGB1, Toll-like receptor 4 (TLR4), nuclear factor-κB P65 (NF-κB P65) and other related signaling pathways were detected by RT-PCR, Western-blot and IHC.

There was no significant difference in the expression of serum leukocyte count, neutrophil count and C-reactive protein between sham operation group and control group (P>0.05). Serum leukocyte count, neutrophil count and C-reactive protein level in sepsis group were significantly higher than those in sham operation group (P<0.05). GA treatment for 72 h significantly decreased the levels of leukocytes, neutrophils and C-reactive protein in serum of rabbits in sepsis group (P<0.05). The serum creatinine and urea nitrogen levels of rabbits in sepsis group were significantly higher than those in sham operation group (P<0.05). GA treatment for 72 h reduced the serum creatinine and urea nitrogen levels of rabbits in sepsis group (P<0.05). Serum levels of HMGB1, TNF-α, IL-1β and IL-6 in sepsis group were significantly higher than those in sham operation group (P<0.05). GA treatment for 72 h reduced the serum levels of HMGB1, TNF-α, IL-1β and IL-6 of rabbits in sepsis group (P<0.05). The levels of TLR4 and NF-κB p65 in renal tissue of rabbits with sepsis were significantly increased. GA treatment significantly inhibited the activation of TLR4/NF-κB signaling pathway.

Glycyrrhizic acid has certain therapeutic value for AKI related to urogenic sepsis, Glycyrrhizic acid may reduce AKI associated with urogenic sepsis by regulating the HMGB1/TLR4/NF-κB signaling pathway.