Defenestration of the sinusoidal endothelial cell in a rat model of cirrhosis

Authors

  • Takashi Mori,

    1. Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602, Japan
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  • Takeshi Okanoue M.D.,

    Corresponding author
    1. Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602, Japan
    • Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602, Japan
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  • Yoshihiko Sawa,

    1. Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602, Japan
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  • Naoki Hori,

    1. Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602, Japan
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  • Masaharu Ohta,

    1. Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602, Japan
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  • Keizo Kagawa

    1. Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Kamigyo-ku, Kyoto 602, Japan
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Abstract

We characterized the structural and immunohistological changes of sinusoidal endothelial cells that occur during cirrhosis in rats made cirrhotic with thioacetamide. Thioacetamide (200 mg/kg body wt) was injected intraperitoneally three times a week into male Wistar rats. Two, 4, 6 and 12 wk later, rat livers were observed under transmission and scanning electron microscopy and regular microscopy and immunostained with laminin and von Willebrand factor (factor VIII-related antigen) antibodies. The diameters and numbers of sinusoidal endothelial fenestrations did not change significantly after 2 wk in the thioacetamide-treated rats; however, they decreased within 4 wk after thioacetamide treatment. A basement membranelike structure in Disse's space was noted 6 wk after thioacetamide treatment. Laminin was detected in Disse's space after 4 wk. In vitro, in cultured sinusoidal endothelial cells, the diameter of sinusoidal endothelial fenestrations was significantly lower at 6 wk in thioacetamide-treated rats. von Willebrand factor was detected in the cytoplasm as granular fluorescence after 6 wk of thioacetamide treatment. These results suggest that as fibrosis develops in cirrhosis, the structural and immunohistochemical characteristics of sinusoidal endothelial cells change. (HEPATOLOGY 1993;17:891–897.)

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