HDAC2 inhibitor CAY10683 demonstrates protective effects in mice with acute liver failure through autophagy enhancement
Objective:To explore the protective mechanism of HDAC2 inhibitor CAY10683 in an acute liver failure mouse model.Methods:C57BL/6 male mice were randomly divided into normal group,model group,CAY10683 group,autophagy inhibitor MRT68921 group and CAY10683/MRT68921 combined group.A mouse model of acute liver failure was induced by D-galactosamine and lipopolysaccharide.Serum and liver samples were obtained.The serum levels of alanine aminotransferase and aspartate aminotransferase were detected.One part of the liver tissue was used for HE staining and electron microscopy,and the other part was used for biochemical detection.Western blotting was used to detect the relative contents of autophagy protein UNC-51-like kinase 1 and malate dehydrogenase 1(MDH1).Results:The CAY10683 increased the level of autophagy in the acute liver failure mouse model and had a protective effect on the mouse liver.The CAY10683 decreased the glucose,pyruvate,lactate,and LDH contents in liver tissues and increased the MDH1 content in liver tissues in acute liver failure mouse model.The MRT68921 increased the glucose,pyruvate,lactate,and LDH contents in liver tissues and decreased the MDH1 content in liver tissues in acute liver failure mouse model.The CAY10682 antagonized the effect of MRT68921.Conclusion:The HDAC2 inhibitor CAY10683 may improve glucose metabolism by increasing autophagy levels in the process of liver failure in mice and has a protective effect on the liver.
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万方数据
维普
