摘要
这评论的目的是在 apoptotic,增生的和分泌活动与变化构画出与胆汁的上皮的词法异质和对肝胃肠激素和肽和肝损伤的不同大小的胆汁管的异构的 pathophysiological 回答有关的最近的调查结果。因为胆汁的上皮细胞(cholangiocytes ) 是人的 cholangiopathies 的目标的识别,胆汁的功能的知识很快正在增加,它被胆汁管的增长 / 损坏在尺寸的一个小范围以内描绘。胆汁的上皮的唯一的解剖,形态学,神经分布和血管形成与在胆汁的树的不同区域以内的 cholangiocytes 的功能一致。在活体内模型[例如,胆汁管结扎( BDL ),部分肝切除术,胆汁酸,四氯化碳( CCl4 )或 alpha-naphthylisothiocyanate ( ANIT )喂]并且在活体内试验性的工具[例如,刚孤立小、大的 cholangiocytes 或肝内胆汁管单位( IBDU )和小、大的鼠科的 cholangiocytes 的主要文化]允许我们表明肝内的胆汁的上皮的词法、功能的异质。这些模型表明了微分分泌活动和异构的 apoptotic 和不同的大小的管的增生的回答。类似于限制为特定的大小的管的 cholangiocyte 增长 / 损害的动物模型,在人的肝疾病,胆汁管损坏支配特定的大小的胆汁管。与肝内的胆汁的上皮的功能的异质有关的未来研究可以与 cholangiopathies 为病人揭示新 pathophysiological 治疗。
The objectives of this review are to outline the recent findings related to the morphological heterogeneity of the biliary epithelium and the heterogeneous pathophysiological responses of different sized bile ducts to liver gastrointestinal hormones and peptides and liver injury/toxins with changes in apoptotic, proliferative and secretory activities. The knowledge of biliary function is rapidly increasing because of the recognition that biliary epithelial cells (cholangiocytes) are the targets of human cholangiopathies, which are characterized by proliferation/damage of bile ducts within a small range of sizes. The unique anatomy, morphology, innervation and vascularization of the biliary epithelium are consistent with function of cholangiocytes within different regions of the biliary tree. The in vivo models [e.g., bile duct ligation (BDL), partial hepatectomy, feeding of bile acids,carbon tetrachloride (CCI4) or α-naphthylisothiocyanate(ANIT)] and the in vivo experimental tools [e.g., freshly isolated small and large cholangiocytes or intrahepatic bile duct units (IBDU) and primary cultures of small and large murine cholangiocytes] have allowed us to demonstrate the morphological and functional heterogeneity of the intrahepatic biliary epithelium.These models demonstrated the differential secretory activities and the heterogeneous apoptotic and proliferative responses of different sized ducts. Similar to animal models of cholangiocyte proliferation/injury restricted to specific sized ducts, in human liver diseases bile duct damage predominates specific sized bile ducts.Future studies related to the functional heterogeneity of the intrahepatic biliary epithelium may disclose new pathophysiological treatments for patients with cholangiopathies.
基金
a grant award from Scott & White Hospital and The Texas A&M University System Health Science Center, a VA Merit Award, a VA Research Scholar Award and the NIH grants DK58411 and DK062975 to Dr. Alpini, by grant awards to Shannon Glaser and Heather Francis from Scott & White Hospital.
关键词
肝内胆上皮
不均匀性
病理机制
治疗
cAMP
Gastrointestinal hormones
Growth factors
Mitosis
Nerves