Effect of dexmedetomidine on necroptosis during liver injury in septic rats

Abstract

Objective To evaluate the effect of dexmedetomidine on necroptosis during liver injury in septic rats. Methods Eighteen SPF adult male Sprague-Dawley rats, weighing 200-220 g, were divided into 3 groups (n=6 each) using a random number table: sham operation group (group SH), sepsis group (group SEP) and dexmedetomidine group (group DEX). Sepsis was induced by cecal ligation and puncture in chloral hydrate-anesthetized rats in SEP and DEX groups.Dexmedetomidine 5 μg/kg was injected via the caudal vein at 1 h before operation in group DEX.Blood samples were collected from the caudal vein at 6 h after operation for determination of serum aspartate amino-transferase (AST) and alanine amino-transferase (ALT) concentrations.The rats were then sacrificed and livers were removed for determination of the level of reactive oxygen species (ROS) in liver tissues (using chemiluminescence assay) and expression of receptor-interacting protein 1 (RIP1), RIP3, mixed lineage kinase domain-like (MLKL), high-mobility group box 1 protein (HMGB1) and dynamin-related protein 1 (Drp1) in liver tissues (by Western blot). Results Compared with group SH, the serum AST and ALT concentrations were significantly increased, the expression of RIP1, RIP3, MLKL, HMGB1 and Drp1 in liver tissues was up-regulated, and the level of ROS in liver tissues was increased in SEP and DEX groups (P<0.05). Compared with group SEP, the serum AST and ALT concentrations were significantly decreased, the expression of RIP1, RIP3, MLKL, HMGB1 and Drp1 in liver tissues was down-regulated, and the level of ROS in liver tissues was decreased in group DEX (P<0.05). Conclusion The mechanism by which dexmedetomidine attenuates liver injury may be related to inhibition of necroptosis in septic rats. Key words: Dexmedetomidine; Sepsis; Liver; Necrosis