Fluctuation of collagen complex from endothelial cells in liver and in serum during hepatic fibrogenesis

为探讨食蟹猴慢性四氯化碳(CCI_4)中毒时肝纤维化形成与内皮基底膜胶原复合体(CEB)水平的关系。每隔4周在腹腔镜下取肝组织。同时采集猴血清，用抗α1(IV)抗体和抗CEB抗体双抗体夹心ELISA法测定血清CEB水平。在实质细胞开始坏死期间(皮下注射CCl_4后2~3个月)，血清CEB水平升高到正常水平的2~3倍。肝小叶内可见含胶原纤维的隔膜。在肝纤维化前期(CCl_4中毒后5~10个月)，血清CEB-s降至正常水平。活检标本中未观察到明显的肝纤维化征象。Disse的间隙看起来缺乏明显的丹沙板层，如在正弦状腔中所见，含有絮状物质。在非间隔性纤维化形成过程中(CCl_43中毒后10个月以上)，毛细血管内皮细胞排列成致密层。内皮细胞内有明显的吞噬小泡。相当数量的肝窦变成了毛细血管。沿窦周隙和纤维性间隔的胶原纤维也增多。面对纤维性间隔的实质细胞表面也有一层连续的致密层。血清CEB水平再次升高，是正常水平的2-3倍。考虑到这些发现，血清CEB水平随着纤维化的进展而平行升高。

The relation of hepatic fibrogenesis and setum level of CEB (Collagen complex from Endothelial Basement membrane) during chronic carbon tetrachliride(CCI_4) intoxication was investigated in crab eating monkeys. Liver tissues were obtained through biopsy under a laparoscope at 4 week interval. Simultaneously, monkey serum was also collected and serum level of CEB was measured by sandwich ELISA using anti alpha1(IV) antibody and anti CEB antibody.During the initial necrosis of parenchymal cells (2 to 3 months after subcutaneous injection if CCl_4, serum level of CEB was elevated to 2 to 3 times as high as normal level. Septa containing collagen fibrils were observed in liver lobules at this period. No basal lamina, however, was found along the endothelial cells.In the prefibrotic stage (5 to 10 months after CCl_4 intoxication), serum level of CEB swas reduced to normal level. No dignificant sign of liver fibrosis was observed in biopsy samples. The space of Disse seens to lack apparent lamina dansa, containing flocculent material as seen in the sinusoidal lumen. The endothelium was fenestrated as seen in normal liver tissue.During nonseptal fibrogenesis (over 10 months after CCl_43 intoxication), the cpillary was lined by continuous endothelial cells with lamina densa. Pinocytotic vesicles were conspicuous in the endothelium. A cosiderable number of liver sinusoids became capillaries. Collagen fibrils were also increased in number along the perisinusoidal space as well as fibrotic septa. The surface of parenchymal cells faced to fibrotic septa were also lined by a continuous lamina densa. Serum level of CEB was again elevated 2 to 3 times as high as normal level.Taking account of these findings, serum level of cEB was elevated in parallel as fibrogenesis progressed.