Okaya Tomohisa, Nakagawa Koji, Kimura Fumio, Shimizu Hiroaki, Yoshidome Hiroyuki, Ohtsuka Masayuki, Morita Yasuhiro, Miyazaki Masaru
Department of General Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
Hepatogastroenterology. 2008 Nov-Dec;55(88):2146-50.
BACKGROUND/AIMS: To explore the mechanisms by which postoperative complications frequently occur in patients with obstructive jaundice, we examined the effects of obstructive jaundice on hepatic microcirculation and Kupffer cell activity in mice.
Common bile duct ligation and division was performed on C57BL/6 mice to induce obstructive jaundice. One and 2 weeks after surgery, sinusoidal perfusion, leukocyte rolling and sticking in the postsinusoidal venules, and diameters of sinusoids containing blood flow were evaluated using intravital microscopy. Kupffer cell phagocytic activity was estimated by the ratio of Kupffer cells that phagocytosed fluorescent-labeled particles to sinusoids containing blood flow.
The sinusoidal perfusion significantly decreased in the jaundiced mice associated with a significant increase in the number of rolling leukocytes and sticking leukocytes. Obstructive jaundice significantly reduced diameters of sinusoids due to Kupffer cell swelling. Kupffer cell phagocytic activity significantly increased in the jaundiced mice associated with enhanced expression of tumor necrosis factor-alpha mRNA in the liver. These data suggest that obstructive jaundice stimulates Kupffer cell to induce inflammatory mediators and leukocyte-endothelial cell interaction.
Leukocyte adhesion and narrowing of sinusoids due to Kupffer cell activation might impede hepatic microcirculation resulting in hypoxic damage of the liver with obstructive jaundice.
背景/目的：为探究梗阻性黄疸患者术后并发症频发的机制，我们检测了梗阻性黄疸对小鼠肝脏微循环和库普弗细胞活性的影响。
对C57BL/6小鼠行胆总管结扎和切断术以诱导梗阻性黄疸。术后1周和2周，采用活体显微镜评估肝血窦灌注、肝血窦后微静脉中白细胞的滚动和黏附以及有血流的肝血窦直径。通过吞噬荧光标记颗粒的库普弗细胞与有血流的肝血窦的比例来评估库普弗细胞的吞噬活性。
黄疸小鼠的肝血窦灌注显著降低，同时滚动白细胞和黏附白细胞的数量显著增加。由于库普弗细胞肿胀，梗阻性黄疸显著减小了肝血窦直径。黄疸小鼠的库普弗细胞吞噬活性显著增加，同时肝脏中肿瘤坏死因子-α mRNA的表达增强。这些数据表明，梗阻性黄疸刺激库普弗细胞诱导炎症介质以及白细胞与内皮细胞的相互作用。
库普弗细胞活化导致的白细胞黏附和肝血窦狭窄可能会阻碍肝脏微循环，从而导致梗阻性黄疸时肝脏的缺氧损伤。
