The protective effect of Protectin DX on acute liver injury induced by sepsis in mice and the underlying mechanism

Abstract

Objective To explore the effect of Protectin DX(PDX) on acute liver injury(ALI) induced by sepsis in mice and the underlying mechanism. Methods Mice received cecum ligation and puncture(CLP) to induce sepsis-associated acute liver injury. Male C57BL/6 mice were randomly (random number) divided into 3 groups (n=10 each group): (1) sham group (S group), (2) CLP group and (3) CLP + PDX group (PDX group ). Mice in the PDX group were received PDX 1 μg (intraperitoneal injection). One hour after CLP operation, mice in the S and CLP groups were received equal amounts of saline. The serum and liver tissues were collected at 24 h after CLP. The histological changes of the liver were observed by HE staining. The ALT and AST levels in the serum were assessed by using the automatic biochemical analyzer. The levels of cytokines (TNF-α, IL-6, IFN-γ and IL-10) in the serum were quantified by ELISA. MPO activity in the liver tissues were assessed. Western blot was used to detect the expression of pNF-kB p65 and NF-kB p65 in liver tissues. Results Compared with the S group, HE staining in the CLP group showed disordered hepatic cords, hepatocyte swelling and necrosis, infiltrations of inflammatory cells, congestion and bleeding, and the score of liver injury was increased significantly (P<0.05). Levels of ALT, AST, TNF-α, IL-6, IFN-γ, and IL-10 were increased in the CLP group (P<0.05). The activities of NF-κB and MPO in the liver tissues were obviously enhanced (P<0.05). The levels of liver injury, cytokines (TNF-α, IL-6, IFN-γ), MPO and activities of NF-κB in the CLP+PDX group were significantly decreased when compared with those in the CLP group (P<0.05),while the concentration of IL-10 was significantly increased (P<0.05). Conclusions PDX can alleviate sepsis-induced acute liver injury through inhibiting NF-KB activity in the liver tissues. Key words: Protectin DX; Sepsis; Acute liver injury; NF-κB