Ichida T, Sugitani S, Satoh T, Matsuda Y, Sugiyama M, Yonekura K, Ishikawa T, Asakura H
Department of Internal Medicine III, Niigata University School of Medicine, Japan.
Liver. 1996 Dec;16(6):365-71. doi: 10.1111/j.1600-0676.1996.tb00763.x.
Circulating hyaluronan is mostly derived from lymph, fibroblast and Ito cells in the liver, and more than 90% of hyaluronan is degraded in hepatic sinusoidal endothelial cells. Thus, elevated serum hyaluronan is regarded as an indication of hepatic fibrosis with activated Ito cells and dysfunctional sinusoidal endothelial cells. We studied the distribution of hyaluronan in human liver sinusoids to determine the influences on elevated hyaluronan levels in sera. Histochemical examination was made using hyaluronan-binding protein (HABP) and serial sections of liver tissue for staining of alpha-smooth muscle actin (ASMA) (an indicator of activated Ito cells) and of ulex europaeus agglutinin I lectin (UEA-1) (closely related to hepatic sinusoidal capillarization). Positive staining, indicating the presence of hyaluronan, was noted in fibrous regions around the portal tracts, areas of focal necrosis in the liver parenchyma, and walls of the sinusoids in chronic hepatitis. In this group, hyaluronan-positive areas corresponded to positive ASMA staining and faint staining of UEA-1. On the contrary, in liver cirrhosis, UEA-1-positive areas were essentially identical to hyaluronan-positive areas and to ASMA-negative areas in sinusoidal walls. Hyaluronan and ASMA could be detected in the same areas of sinusoidal walls in chronic hepatitis, but not in liver cirrhosis. Hyaluronan appears to be mainly related to the staining of activated Ito cells in chronic hepatitis. Therefore, we concluded that in chronic hepatitis, the production of hyaluronan was accelerated in Ito cells; however, degradation of hyaluronan by sinusoidal endothelial cells continued. On the contrary, in liver cirrhosis, hyaluronan production decreased in Ito cells, and a marked transformation of sinusoidal endothelial cells with hepatic sinusoidal capillarization indicated loss of the ability to degrade hyaluronan. These different mechanisms in chronic hepatitis and liver cirrhosis may operate in the sinusoidal walls and may cause the elevation of hyaluronan in sera.
循环中的透明质酸主要来源于淋巴、成纤维细胞和肝脏中的贮脂细胞，且超过90%的透明质酸在肝血窦内皮细胞中被降解。因此，血清透明质酸升高被视为肝纤维化的一个指标，提示贮脂细胞激活和血窦内皮细胞功能障碍。我们研究了透明质酸在人肝血窦中的分布，以确定其对血清中透明质酸水平升高的影响。使用透明质酸结合蛋白（HABP）对肝组织连续切片进行组织化学检查，以检测α平滑肌肌动蛋白（ASMA，贮脂细胞激活的指标）和荆豆凝集素I（UEA-1，与肝血窦毛细血管化密切相关）。在门管区周围的纤维区域、肝实质的局灶性坏死区域以及慢性肝炎患者的血窦壁中，均观察到透明质酸阳性染色，提示透明质酸的存在。在该组中，透明质酸阳性区域与ASMA阳性染色及UEA-1弱阳性染色相对应。相反，在肝硬化中，UEA-1阳性区域与透明质酸阳性区域以及血窦壁中的ASMA阴性区域基本一致。在慢性肝炎患者的血窦壁相同区域可检测到透明质酸和ASMA，但在肝硬化患者中则未检测到。在慢性肝炎中，透明质酸似乎主要与激活的贮脂细胞染色有关。因此，我们得出结论，在慢性肝炎中，贮脂细胞中透明质酸的产生加速；然而，血窦内皮细胞对透明质酸的降解仍在继续。相反，在肝硬化中，贮脂细胞中透明质酸的产生减少，血窦内皮细胞向肝血窦毛细血管化的显著转变表明其失去了降解透明质酸的能力。慢性肝炎和肝硬化中的这些不同机制可能在血窦壁中起作用，并可能导致血清中透明质酸升高。
