Bhunchet E, Wake K
Department of Anatomy, Faculty of Medicine, Tokyo Medical and Dental University, Japan.
Hepatology. 1992 Dec;16(6):1452-73. doi: 10.1002/hep.1840160623.
The role of liver mesenchymal cell populations in porcine serum-induced rat liver fibrosis were studied morphologically and immunohistochemically. Five-week-old rats were intraperitoneally injected with porcine serum twice a week and examined at various intervals between 3 and 24 wk after the initial injection. At an early phase, numbers of fibroblasts and extracellular matrix increased in the walls of central veins and in portal and capsular connective tissues. In the walls of central veins, the number of "second-layer cells" (i.e., the fibroblasts located at the second layer of the wall) increased. Connective tissue septa, accompanying some fibroblasts, extended from these interstitial tissues into the hepatic parenchyma, and their foremost edges came into direct contact with the perisinusoidal stellate cells. The sinusoids adjacent to the newly formed septa collapsed and later disappeared; this process resulted in the formation of hepatic limiting plates along the septa. At a more advanced stage, the interstitial fibroblasts and septal cells-which were derived from interstitial fibroblasts and the stellate cells-increased and became multilayered, constructing three-dimensional cell networks. These networks, together with increased collagen fibrils and elastic fibers, constitute the fibrotic dense connective tissue. In the control rat, smooth muscle cells were positive on vimentin, desmin and smooth muscle-alpha-actin staining. The stellate cells, second-layer cells, capsular and portal fibroblasts were shown to be vimentin and desmin positive and smooth muscle-alpha-actin negative. In the fibrotic liver, septal(fibroblastic) cells were vimentin and desmin positive and smooth muscle-alpha-actin negative. We conclude that not only the perisinusoidal stellate cells but also the interstitial fibroblasts, including the second-layer cells, play substantial role in the development of porcine serum-induced septal fibrosis in rat liver.
运用形态学和免疫组织化学方法研究了肝间充质细胞群在猪血清诱导的大鼠肝纤维化中的作用。给5周龄大鼠每周腹腔注射猪血清2次，并在首次注射后的3至24周的不同时间点进行检查。在早期，中央静脉壁、门静脉和包膜结缔组织中的成纤维细胞数量和细胞外基质增加。在中央静脉壁中，“第二层细胞”（即位于壁第二层的成纤维细胞）数量增加。伴有一些成纤维细胞的结缔组织间隔从这些间质组织延伸至肝实质，其最前端与窦周星形细胞直接接触。与新形成的间隔相邻的肝血窦塌陷并随后消失；这一过程导致沿间隔形成肝界板。在更晚期阶段，源自间质成纤维细胞和星形细胞的间质成纤维细胞和间隔细胞数量增加并形成多层，构建三维细胞网络。这些网络与增加的胶原纤维和弹性纤维一起构成纤维化的致密结缔组织。在对照大鼠中，平滑肌细胞波形蛋白、结蛋白和平滑肌α-肌动蛋白染色呈阳性。星形细胞、第二层细胞、包膜和成纤维细胞波形蛋白和结蛋白染色呈阳性，平滑肌α-肌动蛋白染色呈阴性。在纤维化肝脏中，间隔（成纤维细胞）细胞波形蛋白和结蛋白染色呈阳性，平滑肌α-肌动蛋白染色呈阴性。我们得出结论，不仅窦周星形细胞，而且包括第二层细胞在内的间质成纤维细胞在猪血清诱导的大鼠肝间隔纤维化的发展中起重要作用。
