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

肝硬化发病机制研究——特别是肝微循环系统细胞骨架异常——

基本信息

批准号：
60570337
负责人：
ODA Masaya
金额：
$ 0.96万
依托单位：
Keio University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1985
资助国家：
日本
起止时间：
1985 至 1986
项目状态：
已结题

项目摘要

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

肝窦是肝脏微循环系统的主要组成部分，其超微结构特征是存在窦状内皮腔（SEF），即筛板状孔，并且在窦状内皮下没有基底膜。肝组织窦状内皮细胞质和原代单层培养中均存在肌动蛋白、钙调蛋白（钙结合蛋白）和钙离子。透射电镜显示微丝的存在与SEF的质膜密切相关。细胞松弛素B在体内和体外处理可引起SEF的扩张和融合，肌动蛋白丝的丝状结构丧失。去甲肾上腺素和组胺引起的窦血流量减少或乙酰胆碱和异丙肾上腺素引起的窦血流量增加分别使SEF收缩或扩张。这些对生物胺的内皮反应在初级单层培养的血管内皮中重现。上述观察结果表明，在Ca和钙调蛋白存在的情况下，内皮内的肌动蛋白丝可能调控SEF的收缩和扩张，这可能是维持血流稳定和血肝细胞交换的调控机制之一。四氯化碳肝硬化大鼠血清中去甲肾上腺素、组胺和内毒素含量升高，胆汁中内毒素含量升高。氢气清除率法测量的正弦血流量明显减少。在实验性肝硬化和人肝硬化中，SEF的直径和数量都明显减少，并且在窦内皮下出现基底膜，即。肝窦的毛细血管化。肝硬化SEF直径和数量的减少会中断血浆成分和氧从窦状动脉到肝细胞的自由转移，导致肝硬化自我延续的恶性循环。少