Abstract
Objective To evaluate the role of necroptosis in intestinal injury induced by autologous orthotopic liver transplantation (AOLT) in rats. Methods Twenty-four SPF adult male Sprague-Dawley rats, aged 10-12 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 necroptosis inhibitor necrostatin-1 group (group N). Necrostatin-1 1.0 mg/kg and the equal volume of dimethyl sulfoxide (DMSO) were intraperitoneally injected at 30 min before surgery in N and T groups, respectively.Blood samples were collected from the inferior vena cava at 6 h after opening the 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 intestinal fatty acid binding protein (I-FABP) concentrations by enzyme-linked immunosorbent assay.Rats were sacrificed after blood sampling, and the intestine was removed for examination of the pathological changes (with a light microscope) and for determination of malondialdehyde (MDA) contents and superoxide dismutase (SOD) activities (using a spectrophotometer), and the expression of receptor-interacting protein kinase-1 (RIPK1), RIPK3 and mixed lineage kinase domain-like protein (MLKL) in intestinal tissues (by Western blot). Intestinal damage was assessed and scored using Chiu′s scoring system. Results Compared with group S, the serum DAO, D-LA and I-FABP concentrations, MDA content and Chiu′s score were significantly increased, 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 I-FABP concentrations, MDA content and Chiu′s score were significantly decreased, the SOD activity was increased, and the expression of RIPK1, RIPK3 and MLKL was down-regulated in group N (P<0.05). Conclusion Necroptosis is involved in the pathophysiological process of intestinal injury induced by AOLT in rats. Key words: Liver transplantation; Intestine; Necrosis
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