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

肝硬化发病机制和进展的研究——特别是肝窦肌动球蛋白系统

• 批准号: 05670495
• 负责人: ODA Masaya
• 金额: $ 1.41万
• 依托单位: Department of Internal Medicine, School of Medicine, 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: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05670495/
• 关键词: liver cirrhosis; hepatic sinusoidal endothelial cells; hepatic stellate cells (Ito cells); Kupffer cells; Ca^<++> -calmodulin-actomyosin system; electron microscopy; Fura-2AM; FITC labelled endotoxin; prostaglandin (PG) E1; endothelin (ET) -1,3 /

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.

透射电镜和免疫组化显示，肝窦内皮细胞、肝星状细胞（Ito细胞）和枯否细胞中存在肌动蛋白和肌球蛋白纤维以及Ca^++>-钙调蛋白肌动球蛋白系统。Fura 2-AM免疫组化和胞浆内游离Ca^++动态分析表明，Ca^++-钙调蛋白肌动球蛋白系统调节窦内皮窗（SEF）的收缩和扩张，扫描电镜和透射电镜观察显示，与对照组相比，SEF的直径和数量明显减少，定量分析表明，肝硬化时枯否细胞对FITC标记内毒素的吞噬活性明显降低。电镜观察证实，与对照组相比，肠系膜静脉导管注入的微粒在肝硬化肝Disse间隙内减少，提示肝窦血流量减少的加重是由于SEF直径和数量减少以及枯否细胞吞噬活性降低所致。两者均与急性肝损伤时血清内毒素水平升高有关。

项目成果

風本信吾、織田正也、他: "肝類洞内皮細胞の異物処理機能-in vivoおよびin vitroの検討" 肝類洞壁細胞研究の進歩. 6. 33-39 (1994)

Shingo Kazemoto、Masaya Oda 等：“肝窦内皮细胞的异物处理功能 - 体内和体外研究”肝窦壁细胞研究进展 6. 33-39 (1994)。

Funatsu, K., Matsumaru, A., Itsuji, S., Ueno, H., Arakawa, S., Takagi, T., Ebihara, Y., Mizuno, Y., Oda, M.and Ishii, H.: "Hepatocellular injury due to active oxygen radicals produced by rat liver macrophages in vivo and in vitro." Cells of the Hepatic Si

Funatsu, K.、Matsumar, A.、Itsuji, S.、Ueno, H.、Arakawa, S.、Takagi, T.、Ebihara, Y.、Mizuno, Y.、Oda, M. 和 Ishii, H.：

Oda, M.: "Liver Innervation" T. Shimazu, 10 (1996)

Oda, M.：“肝脏神经支配” T. Shimazu，10 (1996)

Oda,M.et al.: "A new aspect of the hepatic microvasculature" Progress in Applied Microcirculation. 19. 25-39 (1993)

Oda,M.et al.：“肝脏微血管系统的新方面”应用微循环进展。

塚田信廣: "肝類洞内皮細胞内のactin, myosin-II, Ca^<++>-ATPaseの局在" 肝細胞骨格研究会誌. 4. 1-11 (1994)

Nobuhiro Tsukada：“肌动蛋白、肌球蛋白-II 和 Ca^++-ATP 酶在肝窦内皮细胞中的定位”，《肝细胞骨架研究会杂志》4. 1-11 (1994)。