Objective: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease. Macrophages are an important cell-mediated immune response in the pathogenesis of NAFLD. However, the dynamic changes of intrahepatic infiltration during the pathogenesis of NAFLD remains unclear. Therefore, this study intends to investigate the changes and their correlations with morphological indicators, hepatic histopathological index, and intrahepatic macrophage infiltration in the progression of NAFLD induced by high-fat diet in mice. Methods: C57BL/6J mice were fed with 42% high-fat diet, and the morphological data and liver tissue were obtained at 1, 2, 4, 8 and 12 months, respectively. Hepatic histopathological characteristics were evaluated by HE stain. Immunohistochemical staining was used to detect the number of F4/80 positive cells in liver tissue at different stages to evaluate the degree of intrahepatic macrophage infiltration. Results: (1) The body weight, liver weight, and liver weight/body weight of mice fed with high-fat diet had gradually increased. (2) HE staining results showed that mice fed with high-fat diet had mainly developed simple steatosis within 1 to 2 months. In addition, a balloon-like hepatocyte degeneration and intralobular inflammation had begun to appear at 4 months, indicating that non-alcoholic steatohepatitis had started, and can be seen very clearly at 8 to 12 months. (3) Immunohistochemical staining results suggested that in the simple steatosis stage of NAFLD, the intrahepatic macrophage infiltration was not significant. However, after NAFLD activity score > 3, a large amount of infiltration had appeared and cluster-like changes in the later stage. (4) Correlation analysis results indicated that the degree of macrophage infiltration was not related to the mice morphological indicators (body weight, liver weight and liver weight/body weight) and pathological indicators (percentage of hepatic steatotic change, and degree of hepatocyte ballooning and intralobular inflammation), but was significantly related to the NAFLD activity score. Conclusion: High-fat diet can successfully induce NAFLD in mice and progress to the stage of non-alcoholic steatohepatitis. At the same time, high-fat diet can induce macrophage infiltration in liver tissue of mice and the changing trend of infiltration is related to NAFLD activity score.
目的： 拟探讨高脂饮食诱导的小鼠非酒精性脂肪性肝病（NAFLD）进展中形态学指标、肝脏组织病理学指标和肝内巨噬细胞浸润的变化及其相关性。 方法： 采用42%的高脂饮食喂养C57BL/6J小鼠，分别于1、2、4、8个月和12个月获取小鼠形态学数据和肝组织，通过HE染色评估肝组织病理学特征，通过免疫组织化学染色检测不同时期肝组织内F4/80阳性细胞数评估肝内巨噬细胞的浸润程度。用单因素方差分析及SNK检验对组间数据进行分析，组间等级资料比较应用秩和检验。 结果： （1）高脂饮食喂养小鼠后其体质量、肝质量和肝质量/体质量均逐渐升高；（2）HE染色结果提示高脂饮食喂养小鼠1～2个月主要形成单纯性脂肪变，而4个月开始出现肝细胞气球样变和小叶内炎症后提示疾病进入非酒精性脂肪性肝炎可能，8～12个月则为十分明确的非酒精性脂肪性肝炎阶段；（3）免疫组织化学染色结果提示肝内巨噬细胞的浸润在NAFLD单纯性脂肪变阶段不明显，而在NAFLD活动度积分>3以后出现大量的浸润，后期甚至呈团簇状改变；（4）相关性分析结果提示巨噬细胞浸润程度与小鼠形态学指标（小鼠体质量、肝质量和肝质量/体质量）和病理学指标（肝细胞脂肪变比例、肝细胞气球样变程度和小叶内炎症）无关，而与NAFLD活动度积分显著相关。 结论： 高脂饮食可以成功诱导小鼠NAFLD，并进展至非酒精性脂肪性肝炎阶段，同时高脂饮食可以诱导小鼠肝组织内巨噬细胞浸润，其浸润的变化趋势与NAFLD活动度积分相关。.
Keywords: Macrophages; Nonalcoholic fatty liver disease; Nonalcoholic steatohepatitis.