遗传 ›› 2022, Vol. 44 ›› Issue (1): 59-67.doi: 10.16288/j.yczz.21-295

• 综述 • 上一篇    下一篇

七鳃鳗胆道闭锁过程中胆汁酸耐受机制研究进展

杨恒1,2(), 逄越1,2(), 李庆伟1,2()   

  1. 1. 辽宁师范大学生命科学学院,大连 116081
    2. 辽宁师范大学七鳃鳗研究中心,大连 116081
  • 收稿日期:2021-08-11 修回日期:2021-09-22 出版日期:2022-01-20 发布日期:2021-11-24
  • 通讯作者: 逄越,李庆伟 E-mail:yangheng199811@163.com;pangyue01@163.com;liqw@263.net
  • 作者简介:杨恒,在读硕士研究生,专业方向:细胞生物学。E-mail: yangheng199811@163.com
  • 基金资助:
    国家自然科学基金项目编号(31772884);国家自然科学基金项目编号(32070518);辽宁省兴辽英才计划领军人才项目编号(XLYC2002093);辽宁省科技项目资助编号(2019-MS-218);辽宁省教育厅项目编号(LJ2020012);大连市科技创新基金项目资助编号(2018J12SN079)

Research progress of bile acids tolerance mechanism in lamprey biliary atresia

Yang Heng1,2(), Pang Yue1,2(), Li Qingwei1,2()   

  1. 1. College of Life Science, Liaoning Normal University, Dalian 116081, China
    2. Lamprey Research Center, Liaoning Normal University, Dalian 116081, China
  • Received:2021-08-11 Revised:2021-09-22 Online:2022-01-20 Published:2021-11-24
  • Contact: Pang Yue,Li Qingwei E-mail:yangheng199811@163.com;pangyue01@163.com;liqw@263.net
  • Supported by:
    Supported by the National Natural Science Foundation of China Nos(31772884);Supported by the National Natural Science Foundation of China Nos(32070518);Liaoning Climbing Scholar, the Distinguished Professor of Liaoning No(XLYC2002093);the Program of Science and Technology of Liaoning Province No(2019-MS-218);the Project of the Educational Department of Liaoning Province No(LJ2020012);the Science and Technology Innovation Fund Research Project of Dalian City No(2018J12SN079)

摘要:

胆道闭锁(biliary atresia, BA)是一种罕见的婴幼儿肝胆疾病,其特征是纤维硬化性胆管病变,导致肝外胆管和肝内胆管阻塞或闭塞,胆汁不能向肠道排泄,胆汁酸对肝实质细胞造成严重损伤,最后导致肝硬化和肝衰竭危及生命。目前,胆道闭锁的发病机理尚不明确,临床上普遍采用“先葛西”、“后移植”的序贯性治疗方式。葛西手术(Kasai)通过建立胆汁引流通道从而延长患儿自体肝生存时间,但随着门静脉高压和原发性胆管炎等并发症的出现,最后患者仍需要肝移植来挽救生命。七鳃鳗(lamprey)是唯一在生长发育过程中胆管能够自发消失的脊椎动物,在幼体期七鳃鳗具有完整的胆道系统,但在变态过程中,七鳃鳗表现出发育性胆道闭锁,胆管及胆囊逐渐退化直至整个胆道系统完全丧失,同时肝细胞发生重排和精细结构改变。研究发现,七鳃鳗可以在变态发育过程中形成胆道闭锁症状时维持血浆正常的胆汁酸水平,从而不会发生肝硬化和肝衰竭,适应性地在胆道闭锁和胆汁淤积症中存活。为探究七鳃鳗胆汁酸耐受在胆道闭锁疾病中的应用,本文对近年来七鳃鳗发生胆道闭锁而产生对胆汁酸耐受机制的相关研究进展进行了总结,以期为人类胆道闭锁疾病的诊断和治疗提供参考。

关键词: 七鳃鳗, 变态发育, 胆道闭锁, 胆汁淤积, 耐受机制

Abstract:

Biliary atresia (BA) is a rare biliary disease in infants and young children, which is characterized by fibrosclerotic bile duct disease, leading to extrahepatic and intrahepatic bile duct obstruction or occlusion. The bile acids cannot be excreted to the intestinal tract, which causes serious damage to the liver parenchyma cells, and eventually leads to life-threatening cirrhosis and chronic liver failure. At present, the pathogenesis of biliary atresia is unknown. The sequential treatment of “first Gexi” and “later transplantation” is nowadays widely adopted in the clinic. Gossi operation (Kasai) can prolong the survival time of autologous liver by the establishment of bile drainage channel. However, it is necessary for patients to perform liver transplantation with the emergence of complications such as portal hypertension and primary cholangitis. Lampreys are the only vertebrates whose bile duct can disappear spontaneously in the process of growth and development. Lampreys have complete biliary system at the larval stage, but in the process of metamorphosis, lampreys show developmental biliary atresia, bile duct and gallbladder gradually degenerate until the whole biliary system is completely lost, and hepatocytes undergo rearrangement and fine structural changes at the same time. It has been found that lampreys can maintain normal plasma bile acid levels when the symptoms of biliary atresia are formed in during metamorphosis, so that liver cirrhosis and hepatic failure do not occur, thereby adapting to and surviving biliary atresia and cholestasis. To explore the application of bile acids tolerance in biliary atresia, we summarize the recent research progress on the mechanism of bile acids tolerance caused by biliary atresia in lampreys, and further provide a reference for the development of diagnosis and treatments of human biliary atresia.

Key words: lampreys, metamorphosis, biliary atresia, cholestasis, tolerance mechanism