Effect of ethyl pyruvate on renal high mobility group box-1 protein expression and acute kidney injury in rats with delayed resuscitation after thermal injury

Abstract

To investigate the effect of ethyl pyruvate (EP) on high mobility group box-1 protein (HMGB1) expression in renal tissue and acute kidney injury in rats with delayed resuscitation after thermal injury. Seventy-eight Wistar rats subjected to 30% total body surface area full-thickness thermal injury followed with delayed resuscitation were divided into 3 groups: sham group (n = 18), injury group (n = 30) and EP group (n = 30). Renal tissue and blood samples were harvested to determine HMGB1 mRNA as well as its protein expression and renal function parameter at the 8, 24, 72 h post the "injury". HMGB1 mRNA was semi-quantitatively measured by reverse transcription polymerase chain reaction taking GAPDH as an internal standard, and HMGB1 protein expression was determined by Western blot and immunohistochemistry. Blood urea nitrogen (BUN) levels were measured with automatic biochemistry analyzer. The pathological changes of renal tissues were examined using HE staining. Compared with sham controls, both mRNA and protein expressions of HMGB1 in injury group were significantly enhanced in kidneys at 8 - 72 h after thermal injury (P < 0.05), meanwhile serum BUN levels were markedly increased (P < 0.05). Compared with injury group, the renal HMGB1 mRNA and protein expressions were markedly down-regulated in EP group at 8 h, 24 h and 72 h post injury (P < 0.05), respectively, and meanwhile serum BUN levels were reduced significantly (P < 0.05). Inflammatory cell infiltration was found in renal tissues following injury, and kidney injury was markedly alleviated after treatment with EP. It indicated that HMGB1 appears to be involved in the pathogenesis of post-burn acute kidney injury. Treatment with EP reduces renal HMGB1 expression, and protects against acute kidney injury secondary to delayed resuscitation after major burns.