Department of Radiology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, Japan.
Gut. 2010 Feb;59(2):258-66. doi: 10.1136/gut.2009.176651. Epub 2009 Nov 16.
The pathogenesis of non-alcoholic fatty liver disease (NAFLD) is incompletely understood. Kupffer cells (KCs), phagocytic liver-resident macrophages, provide a protective barrier against egress of endotoxin from the portal to the systemic circulation. It is not known if KC phagocytic function is impaired in NAFLD. Super-paramagnetic iron oxide (SPIO) magnetic resonance imaging is a comparative technology dependent on KC phagocytic function.
To evaluate KC uptake function, in patients and experimental animals with NAFLD, using SPIO.
Abdominal CT and histological examination of liver biopsy specimens were used to estimate the degree of steatosis in patients with NAFLD and controls with chronic hepatitis C. SPIO-MRI was then performed in all patients. Normal rats fed a methionine-choline-deficient diet to induce non-alcoholic steatohepatitis (NASH), the more severe stage of NAFLD, and obese, insulin resistant, Zucker fa/fa rats with steatohepatitis, were also studied with SPIO-MRI and analysed for hepatic uptake of fluorescent microbeads. Immunohistochemical analysis evaluated the numbers of KCs in patients and rat livers.
Relative signal enhancement (RSE), inversely proportional to KC function, was higher in patients with NAFLD than in controls and with the degree of steatosis on CT. RSE also positively correlated with the degree of steatosis on histology and was similarly higher in rats with induced severe NAFLD (NASH). On immunohistochemistry, defective phagocytic function was the result of reduced phagocytic uptake and not due to reduced KC numbers in rats or patients with NAFLD.
KC uptake function is significantly impaired in patients with NAFLD and experimental animals with NASH, worsens with the degree of steatosis and is not due to a reduction of KC numbers.
非酒精性脂肪性肝病（NAFLD）的发病机制尚不完全清楚。库普弗细胞（KCs）是吞噬性肝驻留巨噬细胞，为防止内毒素从门脉逸出到全身循环提供了一道保护屏障。目前尚不清楚 NAFLD 患者的 KC 吞噬功能是否受损。超顺磁性氧化铁（SPIO）磁共振成像是一种依赖于 KC 吞噬功能的比较技术。
用 SPIO 评估 NAFLD 患者和实验动物的 KC 摄取功能。
通过腹部 CT 和肝活检组织学检查，评估 NAFLD 患者和慢性丙型肝炎对照者的脂肪变性程度。然后对所有患者进行 SPIO-MRI 检查。还对用蛋氨酸-胆碱缺乏饮食诱导的非酒精性脂肪性肝炎（NASH）、NAFLD 更严重阶段的正常大鼠以及伴有脂肪性肝炎的肥胖、胰岛素抵抗的 Zucker fa/fa 大鼠进行了 SPIO-MRI 检查，并分析了肝内荧光微球的摄取情况。免疫组织化学分析评估了患者和大鼠肝内 KC 的数量。
相对信号增强（RSE）与 KC 功能成反比，在 NAFLD 患者中高于对照组，且与 CT 上的脂肪变性程度相关。RSE 与组织学上的脂肪变性程度也呈正相关，在诱导的严重 NAFLD（NASH）大鼠中更高。免疫组织化学显示，在大鼠和 NAFLD 患者中，吞噬功能缺陷是吞噬摄取减少的结果，而不是 KC 数量减少的原因。
NAFLD 患者和 NASH 实验动物的 KC 摄取功能明显受损，且随脂肪变性程度的加重而恶化，而不是 KC 数量减少的结果。
