Protective effect of autophagy in mice with acute liver injury induced by D- galactosamine / lipopolysaccharide and related mechanisms

Objective To investigate the role and mechanism of autophagy in acute liver injury induced by D- galactosamine / lipopolysaccharide( D- Gal N / LPS) in mice.Methods C57 BL /6 mice were used to establish a mouse model of acute liver injury using intraperitoneally injected D- Gal N / LPS.In this animal experiment,the mice were divided into control group,D- Gal N / LPS group,rapamycin + D-Gal N / LPS group,3- MA + D- Gal N / LPS group,and Atg7 siRNA + D- Gal N / LPS group.The survival of the mice was observed,and liver pathological changes were observed to analyze liver injury.An automatic biochemical analyzer was used to measure the serum levels of alanine aminotransferase( ALT) and aspartate aminotransferase( AST),quantitative real- time PCR was performed to measure the mRNA expression of tumor necrosis factorα( TNFα) and interleukin- 6( IL- 6),and a fluorescence microscope was used to observe the apoptosis of hepatocytes.A One- way ANOVA was used for comparison between multiple groups;the least significant difference t- test was used for homogeneity of variance and the Games- Howell method was used for heterogeneity of variance.Results Compared with the D- Gal N / LPS group,the rapamycin + D- Gal N / LPS group had a significant increase in survival rate( 80% vs 40%),significantly reduced liver hemorrhage,inflammation,and necrosis and apoptosis of hepatocytes,and significant reductions in serum levels of ALT( 427.4 ± 195.5 U / L vs977.7 ± 247.3 U / L,P = 0.002) and AST( 378.2 ± 169.7 U / L vs 1100.0 ± 438.0 U / L,P = 0.004),as well as significant reductions in the mRNA expression of TNFα( 0.288 ± 0.010 vs 1.136 ± 0.267,P = 0.003) and IL- 6( 0.272 ± 0.061 vs 0.869 ± 0.317,P =0.010).Compared with the D- Gal N / LPS group,the 3- MA + D- Gal N / LPS group and Atg7 siRNA + D- Gal N / LPS group had significant reductions in survival rate( 0% /10% vs 40%),significantly aggravated liver hemorrhage,inflammation,and necrosis and apoptosis of hepatocytes,and significant increases in serum levels of ALT( 1836.0 ± 560.5 U / L and 1654.0 ± 627.6 U / L vs 977.7 ± 247.3 U / L,P =0.006 and 0.034) and AST( 1948.0 ± 645.5 U / L and 1804.0 ± 492.6 U / L vs 1100.0 ± 438.0 U / L,P = 0.029 and 0.033),as well as significant increases in the expression of TNFα in liver tissue( 2.026 ± 0.342 and 1.994 ± 0.286 vs 1.136 ± 0.267,P = 0.006 and0.005).Conclusion In the mouse model of acute liver injury induced by D- Gal N / LPS,autophagy has an important protective effect,and its regulating mechanism may be associated with the inhibitory effect on inflammatory factors and apoptosis of hepatocytes.