Slott P A, Liu M H, Tavoloni N
Department of Medicine, Mount Sinai School of Medicine, City University of New York, New York.
Gastroenterology. 1990 Aug;99(2):466-77. doi: 10.1016/0016-5085(90)91030-a.
Proliferation of bile duct-like structures is a hepatic cellular reaction observed in most forms of human liver disease and in a variety of experimental conditions associated with liver injury. Yet the origin, means of initiation, and significance of this hyperplasia are unknown. To clarify these issues we induced bile duct proliferation in rats by ligating the common bile duct and studied (a) hepatic incorporation of [3H]thymidine by histoautoradiography, (b) hepatic morphometry, (c) biliary tree volume using [3H]taurocholate as a marker of biliary transit time, (d) immunohistochemical expression of cytokeratin no. 19, (e) the effect of indomethacin, and (f) the role of increased biliary pressure, in the absence of physiological and biochemical evidence of cholestasis, on [3H]thymidine incorporation by the bile-duct cells. The results have demonstrated that (a) the proliferating bile duct-like cells are products of the extant biliary epithelium and retain its characteristics; (b) bile duct cells divide irrespective of the size of the duct in which they are located and form a system with a lumen continuous with the preexisting one; (c) bile duct proliferation results mainly in elongation, not in circumferential enlargement or sprouting of side branches; (d) portal macrophage infiltration does not play a role in the hyperplastic reaction, and (e) increased biliary pressure is the initiating factor in bile duct cell division. Our results provide evidence that under the present conditions, ductular metaplasia of hepatocytes does not occur and there is no functioning stem cell for biliary epithelial growth segregated in any particular duct size or within the portal connective tissue.
胆管样结构的增殖是在大多数人类肝脏疾病形式以及与肝损伤相关的各种实验条件下观察到的一种肝细胞反应。然而，这种增生的起源、起始方式及意义尚不清楚。为阐明这些问题，我们通过结扎胆总管在大鼠中诱导胆管增殖，并研究了：(a) 通过组织放射自显影术检测肝脏对[3H]胸腺嘧啶核苷的摄取；(b) 肝脏形态计量学；(c) 使用[3H]牛磺胆酸盐作为胆汁转运时间标志物的胆管树体积；(d) 细胞角蛋白19的免疫组化表达；(e) 吲哚美辛的作用；以及(f) 在无胆汁淤积的生理和生化证据情况下，胆管压力升高对胆管细胞摄取[3H]胸腺嘧啶核苷的作用。结果表明：(a) 增殖的胆管样细胞是现存胆管上皮的产物并保留其特征；(b) 胆管细胞无论其所在胆管大小如何均进行分裂，并形成一个管腔与先前管腔连续的系统；(c) 胆管增殖主要导致伸长，而非周径增大或侧支芽生；(d) 门静脉巨噬细胞浸润在增生反应中不起作用；以及(e) 胆管压力升高是胆管细胞分裂的起始因素。我们的结果提供了证据，即在当前条件下，肝细胞不会发生小胆管化生，并且在任何特定胆管大小或门静脉结缔组织内均不存在用于胆管上皮生长的功能性干细胞。
