Effect of dexmedetomidine on necroptosis during intestinal injury in rats undergoing autologous orthotopic liver transplantation

Abstract

Objective To evaluate the effect of dexmedetomidine on necroptosis during intestinal injury in rats undergoing autologous orthotopic liver transplantation (AOLT). Methods Twenty-four SPF adult male Sprague-Dawley rats, aged 8-10 weeks, weighing 250-280 g, were divided into 3 groups (n=8 each) using a random number table method: sham operation group (group S), AOLT group (group T) and dexmedetomidine group (group D). Dexmedetomidine 50 μg/kg was intraperitoneally injected at 30 min before surgery in group D. Blood samples were collected from the inferior vena cava at 6 h after opening the hepatic portal vein (at 6 h after the end of surgery in group S) for determination of serum diamine oxidase (DAO), D-lactic acid (D-LA) and tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) concentrations.The intestine was removed for examination of the pathological changes (with a light microscope) and for determination of the level of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity (using spectrophotometry) and expression of receptor-interacting protein kinase-1 (RIPK1), RIPK3, and mixed lineage kinase domain-like (MLKL) in intestinal tissues (by Western blot). Intestinal damage was assessed and scored according to Chiu. Results Compared with group S, the serum DAO, D-LA, TNF-α and IL-10 concentrations, intestinal MDA content and Chiu′s score were significantly increased, the SOD activity was decreased, and the expression of RIPK1, RIPK3 and MLKL was up-regulated in group T (P<0.05). Compared with group T, the serum DAO, D-LA and TNF-α concentrations, intestinal MDA content and Chiu′s score were significantly decreased, the SOD activity and serum IL-10 concentration were increased, and the expression of RIPK1, RIPK3 and MLKL was down-regulated in group D (P<0.05). Conclusion The mechanism by which dexmedetomidine attenuates intestinal injury is related to inhibiting necroptosis in rats undergoing AOLT. Key words: Dexmedetomidine; Liver transplantation; Intestine; Necrosis