Wang Xue-li, Zhang Ling-min, Tang Fu-xing, Guo Zu-wen, Wu Chun-yun, Xiong Zhong-jin
Department of Parasitology, Medical College, Jinan University, Guangzhou 510632.
Zhongguo Ji Sheng Chong Xue Yu Ji Sheng Chong Bing Za Zhi. 2002;20(4):216-9.
To explore possible mechanisms of hepatic fibrosis by investigating the ultrastructural dynamic changes of liver tissue, especially several kinds of cells related to hepatic fibrosis.
Murine schistosomal hepatic fibrosis model was established by infecting mice with Schistosoma japonicum cercariae. Routine transmission electron microscopy was used to observe the liver tissue. H.E. staining was used for examining the pathological changes.
H.E. staining showed that the model was established successfully. Ultrastructural observation showed that at the 6th week after infection, the necrosis of hepatocytes around the acute granulomas occurred; the number of sinusoidal endothelial fenestrae and vitamin A droplets in fat-storing cells decreased; large phagosomes and rough endoplasmic reticulum could be seen in the cytoplasm of Kupffer's cells. At the 8th week, steatosis was found in some hepatocytes, some microvilli emerged on a few inter-hepatocytic surfaces and the inter-hepatocytic spaces were enlarged. Large collagen fibrillar bundles filled in the perisinusoidal spaces, and capillarization of hepatic sinusoids was observed. Secretory vesicles filled with collagen fibrils appeared in the cytoplasm of fat-storing cells with large amount of collagenous fiber bundles surround the cells. Rough endoplasmic reticulum increased in Kupffer's cells. At the 10th week, fat-storing cells were activated and transformed into myofibroblasts. At the 12th week, the number of myofibroblasts decreased but that of fibroblasts and fiber cells increased.
Activation of fat-storing cells and transformation from fat-storing cells into myofibroblasts are the critical link in the development of hepatic fibrogenesis following schistosome infection. Kupffer's cells, necrotic hepatocytes and sinusoidal endothelial cells may relate to the activation of fat-storing cells. Capillarization of hepatic sinusoids possibly accelerates the development of hepatic fibrosis.
通过研究肝组织超微结构的动态变化，特别是几种与肝纤维化相关的细胞，探讨肝纤维化的可能机制。
用日本血吸虫尾蚴感染小鼠建立小鼠血吸虫性肝纤维化模型。采用常规透射电子显微镜观察肝组织。苏木精-伊红（H.E.）染色用于检查病理变化。
H.E.染色显示模型成功建立。超微结构观察显示，感染后第6周，急性肉芽肿周围的肝细胞发生坏死；贮脂细胞的窗孔和维生素A滴数量减少；库普弗细胞的细胞质中可见大吞噬体和粗面内质网。第8周，部分肝细胞出现脂肪变性，部分肝血窦壁微绒毛增多，肝血窦壁间隙增宽。肝血窦周围间隙充满粗大的胶原纤维束，可见肝血窦毛细血管化。贮脂细胞的细胞质中出现充满胶原纤维的分泌小泡，细胞周围有大量胶原纤维束。库普弗细胞的粗面内质网增多。第10周，贮脂细胞活化并转化为肌成纤维细胞。第12周，肌成纤维细胞数量减少，但成纤维细胞和纤维细胞数量增加。
贮脂细胞的活化以及从贮脂细胞向肌成纤维细胞的转化是血吸虫感染后肝纤维化发生发展的关键环节。库普弗细胞、坏死肝细胞和肝血窦内皮细胞可能与贮脂细胞的活化有关。肝血窦毛细血管化可能加速肝纤维化的发展。
