Microcirculatory disturbances and cellular changes during progression of hepatic steatosis to liver tumors
Microcirculatory disturbances and cellular changes during progression of hepatic steatosis to liver tumors
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DOI：
10.1177/1535370217738730
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发表时间：
2018-01-01
影响因子：
3.2
通讯作者：
Abshagen, Kerstin
中科院分区：
文献类型：
--
作者：
Liebig, Marie;Hassanzada, Alireza;Abshagen, Kerstin
非酒精性脂肪肝病与代谢综合征密切相关，包括从脂肪变性到脂肪性肝炎的肝脏疾病病理谱，并可进展为纤维化/肝硬化和肝细胞癌。 2013年，描述了一种模拟非酒精性脂肪肝疾病在短时间内从脂肪性肝炎发展为肿瘤且发病率高的小鼠模型。由于微循环障碍在肝脏疾病中起着至关重要的作用，因此评估了脂肪变性-炎症-肿瘤模型对于微循环研究的适用性。在此，我们利用活体显微镜、生化和组织学技术，对脂肪变性-炎症-肿瘤模型中非酒精性脂肪肝疾病进展的形态、微血管、细胞和功能方面提出了全面的看法。小鼠分别在 6 周、12 周和 20 周时出现脂肪性肝炎、轻度纤维化和肝肿瘤。非酒精性脂肪肝疾病进展伴随着疾病严重程度的几个一般方面，如肝脏/体重指数增加、非酒精性脂肪肝疾病活动评分和肝细胞凋亡。活体显微镜分析显示，肝脏微循环发生显着变化，结构改变增加，白细胞粘附增加，营养灌注受损。非酒精性脂肪肝的进一步特征是肝窦密度较低，并在 20 周时显着上升。特征性的微循环变化使该模型成为分析从脂肪变性到肝肿瘤进展过程中微循环的便捷工具。
Non-alcoholic fatty liver disease is closely associated with metabolic syndrome and comprises a pathological spectrum of liver disease ranging from steatosis to steatohepatitis and can progress to fibrosis/cirrhosis and hepatocellular carcinoma. In 2013, a mouse model was described that mimics non-alcoholic fatty liver disease progression from steatohepatitis to tumors in a short time span and with high incidence. As microcirculatory disturbances play a crucial role in liver disease, the suitability of the steatosis-inflammation-tumor model for microcirculatory studies was assessed. Herein, we present a comprehensive view on morphological, microvascular, cellular, and functional aspects of non-alcoholic fatty liver disease progression in the steatosis-inflammation-tumor model using intravital microscopy, biochemical, and histological techniques. Mice develop steatohepatitis, mild fibrosis, and liver tumors at ages of 6, 12, and 20 weeks, respectively. Non-alcoholic fatty liver disease progression was accompanied by several general aspects of disease severity like increasing liver/body weight index, non-alcoholic fatty liver disease activity score, and hepatocellular apoptosis. Intravital microscopic analysis revealed significant changes in hepatic microcirculation with increasing structural alterations, elevated leukocyte adherence, and impaired nutritive perfusion. Non-alcoholic fatty liver disease was further characterized by a lower sinusoidal density with a striking rise at 20 weeks. The characteristic microcirculatory changes make the model a convenient tool for analysis of microcirculation during progression from steatosis to liver tumor.