McCuskey Robert S, Ekataksin Wichai, LeBouton Albert V, Nishida Jiro, McCuskey Margaret K, McDonnell Deboragh, Williams Catherine, Bethea Nancy W, Dvorak Bohuslav, Koldovsky Otakar
Department of Cell Biology and Anatomy, College of Medicine, University of Arizona, Tucson, Arizona 85724, USA.
Anat Rec A Discov Mol Cell Evol Biol. 2003 Nov;275(1):1019-30. doi: 10.1002/ar.a.10117.
The development of hepatic microvascular heterogeneity after birth, and its temporal relationship to the development of parenchymal cell plates have received little attention. As a result, the morphogenesis of some of the parameters contributing to this heterogeneity in suckling and weaned rats was studied as a function of time between postpartum days 4 and 30 using in vivo light microscopic, electron microscopic, and immunocytochemical methods. During the early suckling period, the sinusoid network is highly anastomotic, with little evidence of zonation, and the parenchymal cell plates contain multiple cells and are irregularly arranged throughout the lobule. Sinusoidal endothelial fenestration is sparse at 4 days, but phagocytic Kupffer cell (KC) function already exists and exhibits zonal heterogeneity, with more cells located in the periportal zone. With increasing age, endothelial fenestrae increase and organize as sieve plates. Widened centrilobular radial sinusoids form through a loss ("drop-out") of intersinusoidal sinusoids (ISS). Concomitantly, the associated cell plates straighten and become one cell thick. Hepatocyte DNA synthesis and mitosis are higher in the periportal zone, which retains thickened cell plates and anastomotic sinusoids. The centrilobular sinusoids may widen to accommodate the increased volume of blood that results from the loss of ISS as well as the increased numbers of periportal sinusoids containing flow that feed these vessels. KC phagocytic activity increases during the suckling period concomitant with an increase of gut-derived endotoxin in the portal blood, which suggests that the KCs may be releasing mediators that affect sinusoid diameter, blood flow, endothelial fenestration, and perhaps parenchymal growth either directly or through the stimulation of growth factors.
出生后肝微血管异质性的发展及其与实质细胞板发育的时间关系很少受到关注。因此，利用体内光学显微镜、电子显微镜和免疫细胞化学方法，研究了哺乳和断奶大鼠中导致这种异质性的一些参数的形态发生与出生后第4天至第30天之间时间的关系。在哺乳早期，肝血窦网络高度吻合，几乎没有分区迹象，实质细胞板包含多个细胞，在整个小叶中排列不规则。4天时肝血窦内皮窗孔稀疏，但吞噬性枯否细胞（KC）功能已经存在并表现出区域异质性，更多细胞位于汇管周围区。随着年龄增长，内皮窗孔增加并组织成筛板。通过肝血窦间血窦（ISS）的缺失（“脱落”）形成增宽的中央静脉周围放射状血窦。与此同时，相关的细胞板变直并变为单层细胞厚。门静脉周围区肝细胞DNA合成和有丝分裂较高，该区保留增厚的细胞板和吻合的血窦。中央静脉周围血窦可能增宽以容纳因ISS缺失以及向这些血管供血的含血流的门静脉周围血窦数量增加而导致的血量增加。在哺乳期间，KC吞噬活性增加，同时门静脉血中来自肠道的内毒素增加，这表明KC可能释放直接或通过刺激生长因子影响血窦直径、血流、内皮窗孔以及可能影响实质生长的介质。
