Faculty of Veterinary Medicine, Utrecht University, Yalelaan 104, PO Box 80154, 3508 TD Utrecht, The Netherlands.
Mamm Genome. 2012 Feb;23(1-2):76-84. doi: 10.1007/s00335-011-9364-0. Epub 2011 Nov 4.
Congenital disorders of the hepatic portal vasculature are rare in man but occur frequently in certain dog breeds. In dogs, there are two main subtypes: intrahepatic portosystemic shunts, which are considered to stem from defective closure of the embryonic ductus venosus, and extrahepatic shunts, which connect the splanchnic vascular system with the vena cava or vena azygos. Both subtypes result in nearly complete bypass of the liver by the portal blood flow. In both subtypes the development of the smaller branches of the portal vein tree in the liver is impaired and terminal branches delivering portal blood to the liver lobules are often lacking. The clinical signs are due to poor liver growth, development, and function. Patency of the ductus venosus seems to be a digenic trait in Irish wolfhounds, whereas Cairn terriers with extrahepatic portosystemic shunts display a more complex inheritance. The genes involved in these disorders cannot be identified with the sporadic human cases, but in dogs, the genome-wide study of the extrahepatic form is at an advanced stage. The canine disease may lead to the identification of novel genes and pathways cooperating in growth and development of the hepatic portal vein tree. The same pathways likely regulate the development of the vascular system of regenerating livers during liver diseases such as hepatitis and cirrhosis. Therefore, the identification of these molecular pathways may provide a basis for future proregenerative intervention.
先天性肝门脉血管病变在人类中较为罕见，但在某些犬种中却频繁发生。在犬类中，主要有两种亚型：肝内门体分流，被认为源于胚胎静脉导管的闭合缺陷；以及肝外分流，连接内脏血管系统与腔静脉或奇静脉。这两种亚型都导致门静脉血流几乎完全绕过肝脏。这两种亚型都会损害肝内门静脉树的较小分支的发育，并且向肝小叶输送门静脉血液的终末分支往往缺失。临床症状归因于肝脏生长、发育和功能不良。在爱尔兰猎狼犬中，静脉导管的通畅似乎是一种双基因特征，而具有肝外门体分流的凯恩梗犬则表现出更为复杂的遗传方式。这些疾病的相关基因在散发性人类病例中无法确定，但在犬类中，对外科肝门分流形式的全基因组研究已处于高级阶段。这种犬类疾病可能会发现新的基因和途径，这些基因和途径在肝脏生长和门静脉树发育过程中合作。在肝炎和肝硬化等肝脏疾病中，同样的途径可能调节着再生肝脏的血管系统的发育。因此，这些分子途径的确定可能为未来的促再生干预提供基础。
