Angermüller S, Schunk M, Kusterer K
Department of Anatomy and Cell Biology II, University of Heidelberg, Germany.
Hepatology. 1995 Jun;21(6):1594-601. doi: 10.1002/hep.1840210618.
In the model of the perfused rat liver, we investigated the alterations of sinusoidal cells in the pathogenesis of liver injury caused by hypoxia and reperfusion. In sinusoidal endothelial cells, the activity of xanthine oxidase (XOX), a cytoplasmic marker enzyme, was located cytochemically and determined biochemically. Kupffer cells, identified by their endogenous peroxidase staining, were studied with regard to changes in their ultrastructure. In our experiments, parenchymal cells were shown to be severely damaged in contrast to sinusoidal lining cells, which showed minor signs of injury. In comparison with the control group, XOX activity increased significantly in the sinusoidal endothelial cells after low-flow hypoxia; however, after reoxygenation of only 5 minutes, that activity was lower after hypoxia but higher after control perfusion. In Kupffer cells, hypoxia resulted in a strong suppression of phagocytic and endocytotic activity and in a disappearance of the lamellopodia. Kupffer cells were flattened, resembling sinusoidal endothelial cells. After reoxygenation phagocytic vesicles, lamellopodia, and cell volume of Kupffer cells increased markedly in comparison with the control group. In the hypoxia/reperfusion injury model, our observations revealed significant alterations of sinusoidal lining cells. It appears that sinusoidal endothelial cells respond to the hypoxic phase by producing oxygen-derived free radicals and that Kupffer cells respond to the subsequent reperfusion phase by activation followed by the release of toxic mediators.
在灌注大鼠肝脏模型中，我们研究了缺氧和再灌注所致肝损伤发病机制中肝血窦细胞的变化。在肝血窦内皮细胞中，通过细胞化学定位和生化测定法确定了胞质标记酶黄嘌呤氧化酶（XOX）的活性。通过内源性过氧化物酶染色鉴定的库普弗细胞，对其超微结构的变化进行了研究。在我们的实验中，与肝血窦衬里细胞相比，实质细胞显示出严重损伤，而肝血窦衬里细胞仅表现出轻微损伤迹象。与对照组相比，低流量缺氧后肝血窦内皮细胞中的XOX活性显著增加；然而，仅复氧5分钟后，该活性在缺氧后较低，但在对照灌注后较高。在库普弗细胞中，缺氧导致吞噬和胞吞活性强烈抑制，片状伪足消失。库普弗细胞变扁平，类似于肝血窦内皮细胞。复氧后，与对照组相比，库普弗细胞的吞噬小泡、片状伪足和细胞体积明显增加。在缺氧/再灌注损伤模型中，我们的观察结果显示肝血窦衬里细胞有显著变化。肝血窦内皮细胞似乎通过产生氧自由基对缺氧阶段作出反应，而库普弗细胞似乎通过激活并随后释放毒性介质对随后的再灌注阶段作出反应。
