关键词: 四氯化碳, 肝细胞坏死, 肝细胞凋亡, 肝纤维化

Abstract: Objective　To observe the characteristics of hepatocyte necrosis, hepatocyte apoptosis and hepatic fibrosis in the process of liver injury induced by carbon tetrachloride (CCl4 ).Methods　Sixty male C57BL/6 mice were randomly divided into normal control group, 18 h model group, 4-week model group and 8-week model group, with 15 mice in each group.Acute liver injury and chronic liver injury mice were prepared by subcutaneous injection of carbon tetrachloride-olive oil. The observation time points were 18 h, 4 weeks and 8 weeks, respectively, and the general condition of mice, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), HE staining, TUNEL staining and Sirius red staining of liver tissue were used as the observation indexes to evaluate the characteristics of liver inflammation, hepatocyte apoptosis and liver fibrosis.Results　In 18 h model group, the liver tissue lesions were mainly manifested as acute injury, serum ALT and AST were significantly increased, HE staining showed degeneration and necrosis of a large number of hepatocytes around the central vein, TUNEL positive staining shows no obvious infiltration of inflammatory cells. In the liver tissue, except for the vascular wall, there is no positive staining of collagen fibers.In 4-week model group, liver cell injury was still obvious, serum ALT and AST remained at a high level, HE staining showed a large number of inflammatory cell infiltration in the necrotic area, significant collagen fiber deposition in the liver, and a small number of TUNEL positive apoptotic cells were still visible in the liver tissue. In 8-week group, the body weight of model mice decreased significantly, the ratio of liver to body and spleen to body increased significantly, serum ALT and AST remained at a high level, a large amount of collagen fiber deposition in the liver tissue, a small amount of inflammatory cells infiltrated in the fiber interval, and the number of apoptotic cells with positive TUNEL staining decreased significantly. Conclusion　In CCL4-induced continuous liver injury mouse model, hepatocyte necrosis and apoptosis are the main events of early injury, and with the extension of modeling time, hepatocyte necrosis and apoptosis are gradually reduced, and the main pathological features of liver collagen deposition and fibrosis are aggravated.

Key words: carbon tetrachloride, hepatocyte necrosis, hepatocyte apoptosis, hepatic fibrosis