摘要
胆汁的树的微脉管的供应,仙子胆管丛(PBP ) ,源自肝的动脉树枝和流动进肝窦状隙。PBP 的详细三维的研究被使用扫描电子执行了显微镜学脉管的腐蚀演员组(SEMvcc ) 技术。认为 PBP 在支持胆汁的上皮的能分泌、吸收性的功能起一个基本作用,他们在常态和病理的组织被探索。正常的肝证明 PBP 安排在 extra-附近 -- 并且肝内的胆汁的树。在小门道, PBP 被日益增多地继续了它显示出一个更复杂的脉管的网络的额外的肝的 PBP 的 capillaries 的单个层描绘。在普通的管结扎(BDL ) 以后,胆汁管和 PBP 增长的进步修正被观察。PBP 介绍在许多胆汁管附近安排的一个三维的网络并且作为容器的捆出现,由有典型圆网孔结构的同类的直径的 capillaries 镇静。PBP 网络从显得正常的正弦曲线网络是容易可区分的。在 BDL 期间考虑 PBP 的庞大的延期,脉管的内皮生长因素(VEGF ) 起的可能的作用被评估。VEGF -- A, VEGF-C 和他们的相关受体高度出现了在 BDL 老鼠的增殖的 cholangiocytes 积极的免疫。到象肝的动脉结扎一样的 BDL 老鼠的 anti-VEGF-A 或 anti-VEGF-C 抗体的管理导致了一个减少的胆汁管团。rVEGF 的管理 -- 到 BDL 肝的动脉的 A 绑扎老鼠阻止了 cholangiocyte 增长和 VEGF 的减少 -- 表情作为与 BDL 控制老鼠相比。这些数据处于 cholangiocyte 增长的条件建议胆汁的树的动脉的血供给的角色,例如它发生在长期的胆汁郁积期间。在另一方面, VEGF 作为在 cholangiocytes 和 PBP endothelial 之间的串音的一个工具起的作用建议 VEGF 版本和功能的那操作能为肝的动脉或胆汁的树的损坏描绘的人的病理学的条件代表治疗学的策略。
The microvascular supply of the biliary tree, the peribiliary plexus (PBP), stems from the hepatic artery branches and flows into the hepatic sinusoids. A detailed three-dimensional study of the PBP has been performed by using the Scanning Electron Microscopy vascular corrosion casts (SEMvcc) technique. Considering that the PBP plays a fundamental role in supporting the secretory and absorptive functions of the biliary epithelium, their organization in either normalcy and pathology is explored. The normal liver shows the PBP arranged around extra-and intrahepatic biliary tree. In the small portal tract PBP was characterized by a single layer of capillaries which progressively continued with the extrahepatic PBP where it showed a morecomplex vascular network. After common duct ligation (BDL), progressive modifications of bile duct and PBP proliferation are observed. The PBP presents a three-dimensional network arranged around many bile ducts and appears as bundles of vessels, composed by capillaries of homogeneous diameter with a typical round mesh structure. The PBP network is easily distinguishable from the sinusoidal network which appears normal. Considering the enormous extension of the PBP during BDL, the possible role played by the Vascular Endothelial Growth Factor (VEGF) is evaluated. VEGF-A,VEGF-C and their related receptors appeared highly immunopositive in proliferating cholangiocytes of BDL rats. The administration of anti-VEGF-A or anti-VEGF-C antibodies to BDL rats as well as hepatic artery ligation induced a reduced bile duct mass. The administration of rVEGF-A to BDL hepatic artery ligated rats prevented the decrease of cholangiocyte proliferation and VEGF-A expression as compared to BDL control rats. These data suggest the role of arterial blood supply of the biliary tree in conditions of cholangiocyte proliferation, such as it occurs during chronic cholestasis. On the other hand,the role played by VEGF as a tool of cross-talk between cholangiocytes and PBP endothelial cells suggests that manipulation of VEGF release and function could represent a therapeutic strategy for human pathological conditions characterized by damage of hepatic artery or the biliary tree.
基金
MIUR grants PRIN 2005 (prot. 2005067975_001) to E. Gaudio and Biomedicina, Cluster C04, Progetto n. 5 to E.Gaudio-P.Onori MIUR grants PRIN 2005 (prot.No: 2005067975_002) to D. Alvaro and a VA Research Scholar Award, a VA Merit Award and the NIH grants DK58411 and DK062975 to Gianfranco Alpini