FUNCTIONAL ABNORMALITIES OF SINUSOIDAL ENDOTHELIAL CELLS IN RATS WITH ACUTE LIVER REJECTION
FUNCTIONAL ABNORMALITIES OF SINUSOIDAL ENDOTHELIAL CELLS IN RATS WITH ACUTE LIVER REJECTION
复制标题
急性肝排斥大鼠窦内皮细胞功能异常
作者：
Y. Yokoi;H. Muro;S. Baba
本研究旨在探讨急性排斥反应时肝窦内皮细胞（SEC）功能的变化与受体介导的内吞作用的关系。分别以DA肝移植的刘易斯大鼠和刘易斯肝移植的刘易斯大鼠作为排斥组和对照组进行大鼠原位肝移植。分别于术后1、3、5、7、10 d处死动物。通过应用过氧化物酶-抗过氧化物酶IgG复合物作为配体，对冷冻肝切片上的Fc受体（FcR）进行组织化学染色，并测定FcR活性，即，以FcR染色强度表示的结合配体的能力作为SEC功能的指标进行半定量分析。还测定了透明质酸的血清水平，其通过受体介导的SEC内吞作用从循环中特异性清除，沿着血清总胆红素。术后3天，排斥组SEC的FcR染色强度明显减弱，约为对照组的一半（P < 0.05），术后5天染色消失（P < 0.01）。FcR染色强度的降低，即，FcR活性与血清透明质酸水平升高呈显著正相关（r = -0.77; P < 0.001）。在第3天和第5天，还分别出现内皮细胞增生和血清总胆红素显著升高（P < 0.01）的组织学证据。这些结果表明，与传统指标的异常发展相比，SEC的内吞功能受损发生在急性肝排斥反应的早期阶段。因此，受体介导的SEC内吞功能的测定可能为急性排斥反应的早期诊断提供有用的信息。
The purpose of this study was to determine the changes of hepatic sinusoidal endothelial cell (SEC) function in acute liver rejection with respect to receptor-mediated endocytosis. Orthotopic rat liver transplantation was performed in Lewis rats grafted with DA livers and in Lewis rats grafted with Lewis livers as rejectors and controls, respectively. Animals were killed at 1, 3, 5, 7, and 10 days after the operation. Fc receptors (FcRs) were histochemically stained on frozen liver sections by applying peroxidase-antiperoxidase IgG complex as a ligand, and the FcR activity, i.e., capacity of binding the ligands represented by the FcR staining intensity, was semiquantitatively analyzed as an indicator of SEC function. The serum level of hyaluronic acid, which is specifically cleared from the circulation by receptor-mediated SEC endocytosis, was also assayed, along with the total serum bilirubin. Three days after the operation, the SECs of rejectors showed a significantly weaker FcR staining intensity of about half the value of that seen in the controls (P < 0.05), and staining disappeared after 5 days (P < 0.01). The decrease of FcR staining intensity, i.e., FcR activity, showed a correlation with elevation of the serum hyaluronic acid level (r = -0.77; P < 0.001). Histological evidence of endothelialitis and a significant elevation of total serum bilirubin (P < 0.01) were also present at 3 and 5 days, respectively. These results suggest that impairment of the endocytic function of SECs occurs at an earlier phase of acute liver rejection when compared with development of abnormalities of traditional indicators. Determination of receptor-mediated SEC endocytic functions may thus provide useful information for the early diagnosis of acute rejection.