肝移植缺血再灌注对肝内胆管上皮细胞损伤机制的研究现状  

Study on the Mechanisms of Ischemia-Reperfusion Injury to Cholangiocytes after Liver Transplantation

作　　者：庞丽丽[1] 冯莉[1] 赵娜[1] 李胜富[1] 李璐璐[1] 李永胜[1] 龙丹[1] 李幼平[1] 

机构地区：[1]四川大学华西医学院卫生部移植工程与移植免疫重点实验室,成都610041

出　　处：《中国循证医学杂志》2008年第6期443-455,共13页Chinese Journal of Evidence-based Medicine

基　　金：国家973计划项目(NO.200315504);国家自然科学基金NSFC(30500486);国家教育部创新团队发展计划项目

摘　　要：目的了解肝缺血再灌注(Ischemia and Reperfusion,IR)对人肝内胆管上皮细胞(human Intrahepatic Biliary Duct Cells,hIBDC)损伤机制的研究背景和现状,指导临床相关研究,为深入探讨损伤机制找准切入点,为临床防治提供参考。方法计算机检索PubMed(1970～2007)、中国生物医学文献数据库(CBM,1979～2007),限中英文研究。由两位作者参与文献筛选、资料提取,基于纳入文献性质,分主题作描述性系统评价。结果移植肝IR损伤的研究最早见于1970年,此后逐年增加。共纳入符合纳入标准的文献65篇,含临床研究13篇,基础研究35篇,综述17篇。基础研究以机制研究为主,主要集中在:①胆道与胆管上皮细胞生理;②肝移植IR致IBDC损伤机制;③主要损伤机制包括冷缺血、热缺血、再灌注、胆汁和疏水性胆盐损伤。临床研究主要集中在临床预防研究,包括非手术方法(如灌注液、中药和左旋赖氨酸)及手术方法;临床治疗无重大突破,局限于保守治疗和失败后手术补救。结论①大小hIBDC形态、功能、状态的异质性和肝内外胆道血供的特殊性是IR致胆道损伤的重要物质基础。②笔者发现单纯IR或缺氧再给氧(H/R)可致hIBDC的MHC、MIC、DR4、DR5及各种黏附分子改变。③hIBDC和人肝细胞(human hepatocytes,hHC)相比,不耐冷缺血,更不耐再灌注损伤。④疏水性胆盐能加剧器官保存过程中人、猪胆道系统的损害。⑤由于临床研究文献不多,基线条件和评价指标不统一,结果不能合并,基于目前已有文献,证据强度不够,结论仅供参考。Objective To investigate the research base and current understanding of the mechanism ofischemiareperfusion injury （IR） to intrahepatic cholangiocytes after liver transplantation, so as to identify the key points of the mechanism and provide references for clinical practice. Methods We searched PubMed （1970 to 2007） and CBM（1979 to 2007）. Quality assessment and data collection were performed by two reviewers independently. Since the baseline supplied and the measure were very different, we decided to provide a descriptive summary only. Results The earliest study on liver IR was published in 1970. A total of 65 papers were included. There were 13 on clinical studies, 35 on basic research studies; and 17 review articles. Most basic studies focus on injury mechanism： （1） The physiology of bile ducts and Intrahepatic Biliary Duct Cells（IBDC）; （2） the IR caused injury mechanism of IBDC during or after liver transplantation; （3） the basic injury mechanisms include： cold ischemia, warm ischemia, reperfusion, injury of bile and bile salts. Most clinical studies focused on preventive measures, including surgical and non-surgical approaches. Based on the evidence from basic research, changing the composition and perfusion methods of perfusate and protecting the specific blood supply to biliary ducts and cholangiocytes during the operation were important in preventing or reducing such an injury. Conclusion （1） The heterogeneity of morphology, function, status and the special blood supply in large and small IBDC are important material base. （2） Our own study indicated that simple IR or H/R was able to change the expression of MHC, MIC, DR4, DR5 and other adhesion molecules. （3） Compared to hepatic cells, hIBDC can＇t resist cold ischemia and even worse in tolerating reperfusion injury. （4） Hydrophobic bile salts will could increase the harm to bile ducts during organ preservation. （5） Due to the low quantity and limited quantities of clinical researches, the power of evide

关 键 词：肝移植 IR损伤 胆管上皮细胞 评价 

分 类 号：R657.3[医药卫生—外科学]