Department of Surgery, University of Cincinnati, Cincinnati, Ohio 45267-0558, USA.
J Surg Res. 2011 Jul;169(1):e7-14. doi: 10.1016/j.jss.2011.01.056. Epub 2011 Mar 2.
Nonalcoholic fatty liver disease (NAFLD) refers to an increasingly diagnosed condition involving triglyceride accumulation into hepatocytes resulting in a broad spectrum of liver injury. The progression of NAFLD, a relatively benign condition, to nonalcoholic steatohepatitis (NASH) involves the hepatic infiltration of inflammatory cells and subsequent hepatocellular injury. Ischemia/reperfusion (I/R) injury of the liver is a major complication of liver resection, hepatic trauma, and liver transplantation. To date, there have been no studies that have evaluated the effects of hepatic I/R on models of NASH.
Evaluate the effects of hepatic I/R on a mouse model of NASH.
A mouse model of progressive NASH was developed and evaluated using C57BL/6 mice fed a methionine choline deficient diet for 3, 6, 9, and 12 wk. Mice subsequently underwent 90 min of partial hepatic ischemia with reperfusion of 1, 4, and 8 h. Mice were sacrificed after the indicated periods, and blood and liver samples were taken for analysis.
Mice fed the MCD diet showed a rapid induction of hepatic steatosis, inflammation, and fibrosis by 3 wk that persisted over the 12-wk period of diet, as demonstrated by histologic examination, alanine aminotransferase (ALT), and liver content of myeloperoxidase (MPO). The response to I/R in livers with progressive NASH fed MCD diet for 3, 6, 9, and 12 wk showed marked neutrophil recruitment and hepatocyte necrosis.
These data suggest the inflammatory response from I/R is augmented in livers with NASH histopathology compared with normal liver.
非酒精性脂肪性肝病（NAFLD）是指一种日益被诊断的疾病，其特征是肝细胞内甘油三酯积聚，导致广泛的肝损伤。NAFLD 是一种相对良性的疾病，向非酒精性脂肪性肝炎（NASH）的进展涉及炎症细胞在肝脏中的浸润以及随后的肝细胞损伤。肝脏的缺血/再灌注（I/R）损伤是肝切除术、肝外伤和肝移植的主要并发症。迄今为止，尚无研究评估肝 I/R 对 NASH 模型的影响。
评估肝 I/R 对 NASH 小鼠模型的影响。
采用 C57BL/6 小鼠进行实验，用蛋氨酸胆碱缺乏饮食喂养 3、6、9 和 12 周，建立并评估进展性 NASH 的小鼠模型。随后，小鼠接受 90 分钟的部分肝脏缺血，再灌注 1、4 和 8 小时。在指定时间点后处死小鼠，取血和肝组织样本进行分析。
用 MCD 饮食喂养的小鼠在 3 周时迅速出现肝脂肪变性、炎症和纤维化，这种情况在 12 周的饮食期间持续存在，通过组织学检查、丙氨酸氨基转移酶（ALT）和肝脏髓过氧化物酶（MPO）含量可以证实。在 MCD 饮食喂养进展性 NASH 3、6、9 和 12 周的肝脏中，I/R 反应表现为明显的中性粒细胞募集和肝细胞坏死。
与正常肝脏相比，NASH 组织病理学肝脏中的 I/R 炎症反应增强。
