Study of cells and peptides controling the hepatic sinusoidal blood flow

为了解肝硬化时肝窦微循环的变化，我们进行了以下研究.人正常肝组织和肝硬化组织的研究：与正常肝相比，肝硬化组织中α-平滑肌肌动蛋白（α-SMA）和内皮素-1受体（ET-1 R）沿着肝窦壁的免疫定位显著增加。这些产物主要定位于肝星状细胞（HSC）。与正常肝脏相比，肝硬化大鼠神经末梢数目减少，S-100蛋白免疫定位减少.硫代乙酰胺肝硬化大鼠模型肝脏微循环的研究门静脉注射一氧化氮（NO）抑制剂L-NMMA，引起门静脉压力升高，门静脉和肝脏血流量减少.使用大鼠培养的HSC的体外研究。(1)培养的大鼠HSC对ET-1的加入有收缩反应，而对IL-1 β处理的细胞内NO的升高有舒张反应。此外，与IL-1 β处理前相比，加入IL-1 β后HSC中抗环GMP的免疫荧光强度显著增加。(2)用激光共聚焦显微镜观察了正常肝、肝硬化组和大鼠肝星状细胞中抗α-SMA和抗ET-1 R的免疫荧光强度，发现肝硬化组的抗α-SMA和抗ET-1 R的免疫荧光强度较正常组明显增强。提示肝硬化时HSC的收缩和舒张是通过ET-1和NO而不是通过小叶内神经支配参与的。

We performed the following studies to understand the changes of hepatic sinusoidal microcirculation in liver cirrhosis.1. Studies of human normal liver tissues and cirrhotic liver tissues.Immunolocalization of alpha-smooth muscle actin (alpha-SMA) and endothelin-1 receptor (ET-1R) was significantly increased along the sinusoidal walls in cirrhotic liver compared with normal liver. These products were mainly localized in hepatic stellate cells (HSCs). However, nerve endings and immunolocalization of S-100 protein were markedly decreased in cirrhotic liver compared with normal liver.2. Studies of hepatic microcirculation using a thioacetamide treated rat cirrhosis model.The elevation of the portal pressure and the decrease of the portal and hepatic blood flows were induced by the injection of L-NMMA,which is a nitric oxide (NO) inhibitor, in the portal vein.3. In vitro studies using rat cultured HSCs.(1) Cultured rat HSCs contracted in response to the addition of ET-1, and relaxd in response to the elevation of intracellular NO with interluikin-1 beta treatment. Moreover, immunofluorescent intensity of anti-cyclic-GMP in HSCs was significantly increased after IL-1 beta addition compared with before IL-1 beta treatment.(2) Immunofluorescent intensity of anti-alpha-SMA and anti-ET-1R in HSCs obtained from normal liver and cirrhotic liver or rats was examined with a confocal laser-scanning microscope.Immunofluorescent intensity of these antibodies was significantly increased in HSCs of the cirrhosis group compared with the normal group.Based on these results, the contraction and relaxation of HSCs through ET-1 and NO rather than through intralobular innervation are suggested to be deeply involved in hepatic sinusoidal microcirculation in liver cirrhosis.