Abstract:

Objective To discuss the protective effect of sodium butyrate（NaB） on acute liver injury in the mice induced by lipopolysaccharide（LPS） combined with D-galactosamine（D-Gal）， and to clarify its mechanism. Methods Thirty male Kunming mice were randomly divided into control group， model group， and NaB group， and there were 10 mice in each group. The mice in NaB group were given 200 mg·kg^-1·d^-1 NaB， while the mice in control group and model group were given an equal volume of sterile water. The mice in model group and NaB group were intraperitoneally injected with 20 μg·kg^-1 LPS and 600 mg·kg^-1 D-Gal to induce the acute liver injury models. The body weights and liver weights of the mice in various groups were detcted， and the liver index was calculated. HE staining was used to observe the pathomorphology of liver tissue of the mice in various groups； kits were used to detect the activities of alanine aminotransferase（ALT） and aspartate aminotransferase（AST） in serum， and the activities of total superoxide dismutase（T-SOD） and catalase（CAT）， and the levels of malondialdehyde（MDA） in liver tissue of the mice in various groups； Western blotting method was used to detect the expression levels of nuclear factor E2-related factor 2（Nrf2） and heme oxygenase-1（HO-1） proteins in liver tissue of the mice in various groups. Results There were no significant differences in body weights of the mice among various groups （P>0.05）. Compared with control group， the liver index of the mice in model group was significantly increased （P<0.01）. Compared with model group， the liver index of the mice in NaB group was significantly decreased （P<0.01）. The HE staining results showed that the liver tissue of the mice in control group exhibited normal structure， with clear boundaries of hepatocytes， consistent size， radially arranged around the central vein， and the nucleus located in the center of the cells； in model group， the arrangement of hepatocytes was disordered， the cells were swollen， there were multiple foci of hepatocellular necrosis， inflammatory cell infiltration， and hemorrhage； compared with model group， the cells in NaB group showed improved hepatocellular structure and reduced inflammatory infiltration. Compared with control group， the activities of ALT and AST in serum of the mice in model group were significantly increased （P<0.01）； compared with model group， the activities of ALT and AST in serum of the mice in NaB group were significantly decreased （P<0.05 or P<0.01）. Compared with control group， the activities of T-SOD and CAT in liver tissue of the mice in model group were significantly decreased （P<0.01）， and the level of MDA was significantly increased（P<0.01）； compared with model group， the activities of T-SOD and CAT in liver tissue of the mice in NaB group were significantly increased （P<0.05 or P<0.01）， and the level of MDA was significantly decreased（P<0.01）. The Western blotting results showed that compared with control group， the expression levels of Nrf2 and HO-1 proteins in liver tissue of the mice in model group were significantly decreased （P<0.05）； compared with model group， the expression levels of Nrf2 and HO-1 proteins in liver tissue of the mice in NaB group were significantly increased （P<0.01）. Conclusion NaB has a protective effect on LPS/D-Gal induced acute liver injury in the mice， and its mechanism may be related to the upregulation of the expressions of Nrf2 and HO-1 proteins and the increas of the activity of oxidant enzyme in liver tissue by NaB， thereby reduces the liver oxidative stress level of liver.

Key words: Sodium butyrate, Acute liver injury, Oxidative stress, Nuclear factor E2-related factor 2, Heme oxygenase-1