Studies on pathogenesis and progression of liver cirrhosis -with special reference to the hepatic sinusoidal actomyosin sygtems

通过透射电子显微镜和免疫组织化学观察，在肝窦内皮细胞、肝星状细胞(Ito细胞)和Kupffer细胞中有明显的肌动蛋白、肌球蛋白细丝和钙调素肌球蛋白系统。免疫组织化学和FURA2-AM对胞浆内游离钙离子的动态分析表明，钙调素肌球蛋白系统调节肝窦内皮细胞网孔(SEF)的收缩和扩张、Ito细胞的接触和Kupffer细胞的吞噬活性。扫描和透射电子显微镜显示，随着Disse间隙纤维化的形成，SEF的直径和数量明显减小。此外，经肠系膜静脉导管注入的微粒在肝硬变的Disse间隙较对照组明显减少，提示肝窦血流减少的增强可能是由于SEF的直径和数量减少以及Kupffer细胞吞噬活性降低所致，这两者都与肝硬变患者血清内毒素水平的升高有关。

By transmission electron microscopy and immunohistochemistry, actin and myosin filaments and Ca^<++>-calmodulin actomyosin system are evident in the hepatic sinusoidal endothelial cells, hepatic stellate cells (Ito cells) and Kupffer cells. Immunohistochemistry and the dynamic analysis of intracytoplasmic free Ca^<++> ion using Fura2-AM showed that the Ca^<++> -calmodulin actomyosin system regulates the contraction and dilatation of the sinusoial endothelial fenestrae (SEF), contaction of Ito cells and phagocytotic activities of Kupffer cells.Scanning and transmission electron microscopy revealed that the diameter and numbers of the SEF were significantly decreased concomitant with the fibrosis within the space of Disse in cirrhotic liver.By quantitative analysis, the phagocytotic activity of Kupffer cells against the FITC-labelled endotoxin have been shown to be significantly decreased in cirrhotic liver. Furthermore, electron microscopic observations have proved that the microparticles injected via a mesenteric vein catheter are decreased in space of Disse in cirrhotic liver as compared with control liver.These finding may indicate that the enhancement of a decrease of hepatic sinusoidal blood flow results from a decrease of SEF in diameter and number and a decrease of phagocytotic activity of Kupffer cells, both of which have some relationship with an increase of serum endotoxin levels in cirrhotic liver.