The Mechanism Study Of Acute Liver Injury Induced By Acetaminophen

Objective:Acute liver injury is the common ways of the occurrence and the development of various liver disease and leads to liver failure finally. It is extremely important to establish a animal model which is similar to human acute liver injury pathological process. There are a lot of acute hepatic injury animal model, this experiment focuses on the pathogenesis of acute liver injury in mice caused by APAP. Acetaminophen (APAP) is one of the most widely used drugs to moderate pain and reduce fever. APAP is generally safe in therapeutic doses; however, an overdose of APAP may lead to severe liver damage.Methods:Acute liver injury was induced by APAP which is intraperitoneal injected of 300 mg/kg of. The normal group was given an equivalent volume of saline. Animals were sacrificed at various times after administration of APAP to evaluate the level of aspartate aminotransferase (AST), alanine aminotransferase (ALT) and glutathione(GSH),glutathione peroxidase (GSH-PX). Histopathological changes was observed by hematoxylin and eosin (H&E) staining. The protein extracted from liver tissue were analyzed by Western blotting analysis.Results:According to the evaluation of normal group by light microscopic, a regular morphology of the liver parenchyma was evident. In APAP treated mice, severe sinusoidal congestion and hemorrhage, dilated central vein, severe inflammatory cell infiltration, and degenerated hepatocytes showing perinuclear vacuolization were observed. Especially in the group of mice which is treated with APAP for 4 h showe the most severe necrosis is observed. APAP markedly increased the serum AST and ALT activities at 4h after APAP administration compared with normal group. APAP was significantly reduced GSH and GSH-PX in liver tissue at 4h after APAP administration compared with normal group. Western blotting analyses demonstrated that APAP activated the expression of phosphorylation of JNK and STAT3, The expression of pro-caspase-3 and Bcl-2 protein was significantly reduced, especially at 4 h after APAP administration. JNK expression at 12 h after APAP administration recovered to almost normal group.Conclusion:Acute liver injury can be successfully induced by intraperitoneal injections of 300 mg/kg of APAP. This experiment lays a solid foundation to the continue explore of liver drugs, and can provide a theoretical basis.