| Hepatic fibrosis is the common wound-healing response to chronic liver injury, and involves inflammatory cell infiltration, the abnormal accumulation of collagen fibrils, degeneration and necrosis of hepatocyte, and damages to liver architecture and function. It has been proved by clinical research and experimental work on animals that chronic inflammation is a common feature of chronic hepatitis and chronic liver injury leads to liver cirrhosis. Therefore, understanding the pathological mechanism of hepatic inflammation is important to further investigate the formation mechanism of hepatic fibrosis.There are several experimental fibrosis models established by repeated administration of carbon tetrachloride, bile duct ligation(BDL) and immunological mechanisms. A well-established mouse model of hepatic fibrosis is bile duct ligation in rodents, ligation of the common hepatic duct leads to intrahaptic cholestasis. Cholestasis results in the accumulation of hydrophobic bile acids. As a consequence of this initial injury, hepatic inflammation develops, cell activation, the release of cytokines and chemokines, and, subsequently, the inflammatory cell recruitment to the inflammatory sites, hepatocellular apoptosis and necrosis. Repeated and continuous hepatocellular injury induced liver fibrosis.Here we establish and evaluate cholestatic hepatic fibrosis model induced by bile duct ligation in mouse, and using it as a vivo model to investigate the hepatic inflammation during the process of experimental liver fibrogenesis. In the present study, we determine the inflammation related factor ICAM-1,MCP-1 and MPO to evaluation inflammatory infiltration of liver,and investigate the change of hepatic inflammation. Our data showed that the expression of ICAM-1,MCP-1,and MPO increasing associated with Inflammatory cell infiltration after BDL, and result in liver injury.Fox(forkhead/winged helix transcription factor)proteins are transcriptional factors, designated as the unified symbol for all chordate winged helix/forkhead transcription factors by Forkhead/Winged Helix nomenclature committee, and issued in the year of 2000.This family contains a highly conserved Forkhead region, and play important roles in DNA binding, transcriptional activation and transcriptional inhibition. Despite the highly conserved forkhead box DBD, Fox protein regulation and function vary significantly between families, arising in part from sequence variation outside of the DBD, allowing for differential regulation and functional diversification. Fo protein family members are important for a wide spectrum of biological processes ,by which involved in transcriptional regulation and signal transduction pathway. Studies demonstrated that Foxd1,Foxp3, Foxj1 and Foxo can regulation of immune homeostasis and inflammation response.among them, Foxo factors play a role in inflammation related immunoregulation. The Foxo class of transcription factors consists of four members: Foxo1, 3a, 4 and 6.The main function of Foxo subfamily include regulate the homeostasis of immune-relevant cells, cell cycle arrest and apoptosis ,antagonize oxidative stress, and play critical roles in metabolism. It suggests that:Foxo may play an important role in the hepatitis by participating in hepatic inflammatory response.The dynamic expression of Foxo gene in hepatitis mouse liver tissue were determined by reverse transcription-polymerase chain reaction and real time PCR.The result suggest that :with the development of hepatic inflammation,The expression of Foxo1 significantly decreased in the BDL groups compared to the Sham-operated control group,and the expression changes similar to inflammation indicator ICAM-1, the expression changes of Foxo4 and Foxo6 extremely resemblance, that the mRNA expression significantly increased after BDL 1day and 3 day. these data suggest that Foxo gene may participate in the proceeding of hepatic inflammation and play critical roles in regulating early hepatic fibrogenesis.
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