Zhong L, Xu K S, Deng L
Department of Gastroenterology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.
Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China.
Zhonghua Gan Zang Bing Za Zhi. 2020 Dec 20;28(12):1042-1047. doi: 10.3760/cma.j.cn501113-20190712-00244.
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. 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. (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. 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.
非酒精性脂肪性肝病（NAFLD）是一种常见的慢性肝病。巨噬细胞是NAFLD发病机制中重要的细胞介导免疫反应。然而，NAFLD发病过程中肝内浸润的动态变化仍不清楚。因此，本研究旨在探讨高脂饮食诱导的小鼠NAFLD进展过程中肝内巨噬细胞浸润的变化及其与形态学指标、肝脏组织病理学指数的相关性。将C57BL/6J小鼠喂食42%的高脂饮食，分别在1、2、4、8和12个月时获取形态学数据和肝脏组织。通过HE染色评估肝脏组织病理学特征。采用免疫组织化学染色检测不同阶段肝脏组织中F4/80阳性细胞数量，以评估肝内巨噬细胞浸润程度。（1）喂食高脂饮食的小鼠体重、肝脏重量及肝脏重量/体重逐渐增加。（2）HE染色结果显示，喂食高脂饮食的小鼠在1至2个月内主要发展为单纯性脂肪变性。此外，4个月时开始出现气球样肝细胞变性和小叶内炎症，表明非酒精性脂肪性肝炎已开始，在8至12个月时非常明显。（3）免疫组织化学染色结果表明，在NAFLD单纯性脂肪变性阶段，肝内巨噬细胞浸润不明显。然而，在NAFLD活动评分>3后，后期出现大量浸润并呈簇状改变。（4）相关性分析结果表明，巨噬细胞浸润程度与小鼠形态学指标（体重、肝脏重量和肝脏重量/体重）及病理学指标（肝脂肪变性改变百分比、肝细胞气球样变程度和小叶内炎症程度）无关，但与NAFLD活动评分显著相关。高脂饮食可成功诱导小鼠发生NAFLD并进展至非酒精性脂肪性肝炎阶段。同时，高脂饮食可诱导小鼠肝脏组织巨噬细胞浸润，浸润的变化趋势与NAFLD活动评分有关。
