Geerts A, Lazou J M, De Bleser P, Wisse E
Laboratory for Cell Biology and Histology, Vrije Universiteit Brussel, Belgium.
Hepatology. 1991 Jun;13(6):1193-202.
In this study, we have investigated the cell population kinetics of fat-storing cells in livers of rats intoxicated with CCl4. Fat-storing cells were identified in cryostat sections by immunoperoxidase staining of desmin. The peroxidase label was visualized using diaminobenzidine/hydrogen peroxide containing Ni2+ and Co(2+)-ions (Nico/diaminobenzidine method). In normal rats, we found 12.8 fat-storing cells/0.1 mm2 in periportal areas vs. 9.4 in pericentral fields. After one injection of CCl4, the number of pericentral cells increased gradually to reach a maximum of 39.4 cells/0.1 mm2 96 hr after injection. The desmin staining intensity of the pericentral fat-storing cells increased from 48 hr onward. At 72 to 120 hr, strongly stained cells were observed in pericentral areas and in bands of tissue between adjacent central veins, reminiscent of the connective tissue septa in fibrotic livers. In the periportal areas the number of fat-storing cells was not altered. After a second and third injection of CCl4, the number of cells increased further in the pericentral areas. When more than three injections were given, the pericentral fat-storing cell population reached a new steady state with the cell number being seven times higher than in control animals. Proliferation of fat-storing cells at different stages of CCl4 intoxication was studied by intravenous administration of 3H-thymidine, followed by combined desmin staining and autoradiography. Autoradiographical labeling of fat-storing cells was nearly absent in control animals and at 24 hr after a single CCl4 injection. At 48 to 96 hr, labeling indices of pericentral fat-storing cells were significantly higher than in control animals, with a maximum at 72 hr when 22.9% of the cells were labeled. After multiple injections of CCl4, labeling indices between 4.9% and 8.4% were found. We conclude that fibrogenesis is preceded by a strong expansion of the fat-storing cell population in the pericentral areas of the liver lobules and in bands of tissue between adjacent central veins. Local proliferation is an important mechanism underlying the expansion of this cell population.
在本研究中，我们调查了四氯化碳中毒大鼠肝脏中贮脂细胞的细胞群体动力学。通过结蛋白的免疫过氧化物酶染色在低温切片中鉴定贮脂细胞。使用含Ni2+和Co(2+)离子的二氨基联苯胺/过氧化氢（Nico/二氨基联苯胺法）使过氧化物酶标记显色。在正常大鼠中，我们发现门周区域每0.1mm2有12.8个贮脂细胞，而中央周围区域为9.4个。单次注射四氯化碳后，中央周围细胞数量逐渐增加，在注射后96小时达到最大值，即每0.1mm2有39.4个细胞。中央周围贮脂细胞的结蛋白染色强度从48小时起增加。在72至120小时，在中央周围区域和相邻中央静脉之间的组织带中观察到强染色细胞，这让人联想到纤维化肝脏中的结缔组织间隔。在门周区域，贮脂细胞的数量没有改变。第二次和第三次注射四氯化碳后，中央周围区域的细胞数量进一步增加。当注射超过三次时，中央周围贮脂细胞群体达到一个新的稳态，细胞数量比对照动物高七倍。通过静脉注射3H-胸腺嘧啶核苷，随后进行结蛋白染色和放射自显影相结合的方法，研究了四氯化碳中毒不同阶段贮脂细胞的增殖情况。对照动物和单次注射四氯化碳后24小时，贮脂细胞的放射自显影标记几乎不存在。在48至96小时，中央周围贮脂细胞的标记指数显著高于对照动物，在72小时达到最大值，此时22.9%的细胞被标记。多次注射四氯化碳后，标记指数在4.9%至8.4%之间。我们得出结论，在肝小叶中央周围区域和相邻中央静脉之间的组织带中，贮脂细胞群体的强烈扩增先于纤维化的发生。局部增殖是该细胞群体扩增的重要机制。
