STUDIES ON THE PATHOGENESIS OF LIVER CIRRHOSIS-WITH SPECIAL REFERENCE TO THE CYTOSKELETAL ABNORMALITIES IN THE HEPATIC MICROCIRCULATORY SYSTEM-

肝窦是肝脏微循环系统的主要组成部分，其超微结构特征是肝窦内窗(SEF)的存在，即筛板状孔，而肝窦内皮下无基底膜。在肝组织和原代单层培养中，肌动蛋白、钙调蛋白(钙结合蛋白)和钙离子(Ca)位于肝窦内皮细胞的胞浆中。透射电子显微镜显示与SEF质膜紧密相连的微丝的存在。在体内和体外用细胞松弛素B处理后，SEF扩张和融合，肌动蛋白细丝结构丢失。对去甲肾上腺素和组胺引起的窦性血流量减少或乙酰胆碱和异丙肾上腺素的增加，SEF分别收缩或扩张。这些内皮细胞对…的反应原代单层培养的肝窦内皮细胞产生更多的生物胺。上述结果提示，在钙和钙调蛋白存在的情况下，SEF的收缩和扩张可能受内皮细胞内肌动蛋白细丝的调节，这可能有助于维持恒定的正弦血流和血-肝细胞交换的调节机制。在四氯化碳诱导的肝硬变中，血清去甲肾上腺素、组胺和内毒素含量升高，胆汁内毒素含量也增加。氢气清除法测得的正弦血流量明显减少。在实验性和人类肝硬变中，随着肝窦内皮下基底膜的出现，SEF的直径和数目均显著减少，即肝窦的毛细血管形成。肝硬变时SEF直径和数目的减少，将阻断血浆成分和氧从肝窦到肝细胞的自由传递，导致肝硬变自发性的恶性循环。较少

The hepatic sinusoids, the major component of the microcirculatory system in the liver, are ultrastructually characterized by the presence of the sinusoidal endoyhelial fenestras(SEF) i.e.the sieve plate-like pores and by the absence of the basement membrane beneath the sinusoidal endothelia. Actin and calmodulin (Ca -binding protein) and calcium ions(Ca ) were proved in the cytoplasm of the sinusoidal endotelium in liver tissue and in primary monolayer culture. Ttansmission electron microscopy revealed the presence of microfilaments in close association with the plasma membrane of the SEF. The in vivo and in vitro treatment with cytochalasin B caused the dilatation and fusion of the SEF with the loss of filamentous structures of actin filaments. the SEF were contracted or dilated respectively in response to a decrease in the sinusoidal blood flow induced by norepinephrine and histamine administration or to an increase by acetylcholine and isoproterenol. These endotelial responses toth … More e biogenic amines were reproduced in the primary monolayer-cultured sinusoidal endothelia. The above observation indicate that the contraction and dilatation of the SEF possibly regulated by actin filaments within the endothelium in the presence of Ca and calmodulin would contribute to the regulatory mechanism for maintaining the constant sinusoidal flow as well as the blood-hepatocyte exchange.In carbon tetrachloride-induced liver cirrhosis,norepinephrine,histamine and endotoxin content in serum were elevated and endotoxin content in bile was also increased. The sinusoidal blood flow measured by hydrogen gas clearance method was significantly reduced. In experimental and human liver cirrhosis, the SEF were significantly reduced both in diameter and in number with the appeartance of the basement membrane beneath the sinusoidal endothelia,i.e.the capillarization of hepatic sinusoids. The decrease of the SEF in diameter and number in cirrhosis would interrupt the free transition of plasma constituents and oxygen from the sinusoids to the hepatocytes, leading to a vicious cycle in the self-perpetuation of liver cirrhosis. Less