Role of necroptosis in liver injury in septic rats

Abstract

Objective To evaluate the role of necroptosis in liver injury in septic rats. Methods Twenty-four SPF healthy male adult Sprague-Dawley rats, weighing 200-220 g, aged 6-8 weeks, were divided into 3 groups (n=8 each) using a random number table: sham operation group (Sh group), sepsis group (Sep group) and specific necroptosis inhibitor necrostatin-1 group (N group). Sepsis was induced by cecal ligation and puncture in anesthetized rats in N and Sep groups.Necrostatin-1 1.0 mg/kg was intravenously injected at 1 h before operation in group N, while the equal volume of dimethyl sulfoxide was given instead in group Sep.Rats were sacrificed at 6 h after operation, and livers were removed for examination of the pathological changes (with a light microscope) and for determination of the level of reactive oxygen species (ROS) in liver tissues (by using chemiluminescence assay) and expression of receptor-interacting protein kinase-1 (RIPK1), RIPK3, mixed lineage kinase domain-like (MLKL) and high-mobility group box 1 protein (HMGB1) in liver tissues (using Western blot). Results Compared with Sh group, the ROS level in liver tissues was significantly increased, and the expression of RIPK1, RIPK3, MLKL and HMGB1 in liver tissues was up-regulated in Sep and N groups (P<0.05). Compared with Sep group, the ROS level in liver tissues was significantly decreased, and the expression of RIPK1, RIPK3, MLKL and HMGB1 in liver tissues was down-regulated in group N (P<0.05). The pathological changes of liver tissues were significantly attenuated in group N when compared with group Sep. Conclusion Necroptosis is involved in liver injury in septic rats. Key words: Sepsis; Liver; Necrosis