Alison M, Golding M, Lalani E N, Nagy P, Thorgeirsson S, Sarraf C
Department of Histopathology, Royal Postgraduate Medical School, London, UK.
J Hepatol. 1997 Feb;26(2):343-52. doi: 10.1016/s0168-8278(97)80051-7.
BACKGROUND/AIMS: Biliary epithelial cells (ductular oval cells) migrate into the periportal and midzonal parenchyma when hepatocyte regeneration after injury is significantly impeded. The potential of oval cells to differentiate into hepatocytes has been questioned. We have sought to resolve this issue using the modified Solt-Farber procedure in which 2-acetylaminofluorene is used to block hepatocyte regeneration in partially hepatectomized rats.
Rats received 2-acetylaminofluorene by oral gavage for 6 days before and up to 7 days after a two-thirds hepatectomy. The cellular reaction was visualized by the immunohistochemical localization of intermediate filaments cytokeratins 8 and 19 and vimentin, cytochrome P450 enzymatic proteins and alpha-foetoprotein. Expression of albumin and alpha-foetoprotein mRNA transcripts were observed in situ using antisense riboprobes.
During the first 9 days after partial hepatectomy long strings of ductular cells spread outwards from the portal areas. These cells exhibited strong diffuse cytoplasmic staining with the anticytokeratin 8 and 19 antibodies, like authentic bile ducts, but in addition also expressed vimentin and alpha-foetoprotein (protein and mRNA)-collectively termed the "oval cell phenotype". Thereafter, these ducts rapidly vanished to be replaced by basophilic hepatocytes which lacked the oval cell phenotype, but which acquired strong expression of albumin mRNA. At 14 days after partial hepatectomy the oval cell phenotype was restricted to the peripheral margins of the newborn periportal hepatocytes, the distal tips of the oval cell ducts, and these too had disappeared within another 7 days.
Ductular oval cells will differentiate into hepatocytes under appropriate experimental conditions.
背景/目的：当损伤后肝细胞再生受到显著阻碍时，胆管上皮细胞（小胆管卵圆细胞）会迁移至汇管区和中区实质。卵圆细胞分化为肝细胞的潜能一直备受质疑。我们试图通过改良的索尔特-法伯程序来解决这一问题，该程序中使用2-乙酰氨基芴来阻断部分肝切除大鼠的肝细胞再生。
大鼠在三分之二肝切除术前6天及术后长达7天经口灌胃给予2-乙酰氨基芴。通过中间丝细胞角蛋白8和19、波形蛋白、细胞色素P450酶蛋白及甲胎蛋白的免疫组化定位观察细胞反应。使用反义核糖探针原位观察白蛋白和甲胎蛋白mRNA转录本的表达。
部分肝切除后的前9天，小胆管细胞长链从汇管区向外伸展。这些细胞与真正的胆管一样，用抗细胞角蛋白8和19抗体染色时呈现强烈的弥漫性胞质染色，但此外还表达波形蛋白和甲胎蛋白（蛋白质和mRNA），统称为“卵圆细胞表型”。此后，这些胆管迅速消失，被缺乏卵圆细胞表型但白蛋白mRNA表达强烈的嗜碱性肝细胞取代。部分肝切除术后14天，卵圆细胞表型局限于新生汇管区肝细胞的周边边缘、卵圆细胞胆管的远端末梢，而这些在另外7天内也消失了。
在适当的实验条件下，小胆管卵圆细胞会分化为肝细胞。
