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

研究了食蟹猴慢性四氯化碳（CCI_4）中毒过程中肝纤维化与CEB（内皮基膜胶原复合物）水平的关系。每隔4周在腹腔镜下活检肝组织。同时采集猴血清，采用抗α 1（IV）抗体和抗CEB抗体夹心ELISA法测定血清CEB水平。在皮下注射CCl_4后2 ~ 3个月的实质细胞坏死初期，血清CEB水平升高至正常水平的2 ~ 3倍。肝小叶中可见含有胶原原纤维的隔层。内皮细胞周围未见基底层。在CCl_4中毒后5 ~ 10个月的纤维化前期，血清CEB水平降至正常水平。活检标本未见明显肝纤维化征象。椎间盘间隙缺乏明显的层状纤维，在窦状腔内可见絮状物质。内皮与正常肝组织一样开孔。在非间隔纤维形成过程中（CCl_43中毒后10个月以上），毛突被连续的内皮细胞排列，呈层状致密。内皮细胞内可见明显的胞浆性囊泡。相当数量的肝窦变成了毛细血管。沿窦周间隙和纤维化间隔的胶原原纤维数量也增加。面向纤维化间隔的实质细胞表面也有连续的层状致密排列。血清CEB水平再次升高至正常水平的2 ~ 3倍。考虑到这些发现，血清cEB水平随着纤维形成的进展而升高。

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.