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

摘要： 目的　观察四氯化碳致肝损伤过程中肝细胞坏死、肝细胞凋亡与肝纤维化的特点。方法　将60只雄性 C57BL/6小鼠随机分为正常对照组、18 h造模组、4 周造模组和8 周造模组,每组各15只。 采用皮下注射四氯化碳 橄榄油方法制备急性肝损伤和慢性肝损伤模型,分别以造模18 h、4周和8周作为观察时间点,以小鼠一般情况、血 清丙氨酸氨基转移酶(ALT)及天冬氨酸氨基转移酶(AST)检测、肝组织HE染色、TUNEL染色和天狼星红染色为观 测指标,评价肝炎症、肝细胞凋亡与肝纤维化特征。结果　造模18 h组肝组织病变以急性损伤表现为主,血清 ALT、AST显著升高,HE染色可见小叶中央静脉周围的大量肝细胞变性、坏死,病变区域大量肝细胞发生凋亡,呈 TUNEL阳性染色,炎性细胞浸润不明显,肝组织内除血管壁外,无胶原纤维阳性染色。造模4周组,肝细胞损伤表 现仍然较为明显,血清ALT、AST保持在较高水平,HE染色显示坏死区域有大量炎性细胞浸润,肝组织出现显著胶 原纤维沉积,肝组织内仍可见到少量TUNEL染色阳性的凋亡细胞。造模8周组,模型小鼠体质量明显减轻,肝体 比、脾体比明显增加,血清ALT、AST仍保持在较高水平,肝组织大量胶原纤维沉积,纤维间隔处有少量炎性细胞浸 润,TUNEL染色阳性的凋亡细胞数量明显减少。结论　四氯化碳诱导的连续性肝损伤小鼠模型中,肝细胞坏死和 凋亡是早期损伤的主要事件,随着造模时间延长,肝细胞坏死和凋亡逐渐减轻,而肝胶原沉积和纤维化加重成为主 要病理特征。

关键词: 四氯化碳, 肝细胞坏死, 肝细胞凋亡, 肝纤维化