胆盐在肝移植术后缺血性胆道病变中的作用及研究进展

刘汉林; 代鑫; 肖奕君; 吴畏

doi:10.3969/j.issn.1674-7445.2022.04.019

胆盐在肝移植术后缺血性胆道病变中的作用及研究进展

doi: 10.3969/j.issn.1674-7445.2022.04.019

610083 成都，中国人民解放军西部战区总医院麻醉疼痛科（刘汉林、吴畏），普通外科（代鑫）；成都医学院（肖奕君）

基金项目:

四川省科技计划项目 2018RZ0135

四川省科技计划项目 2016JQ0023

详细信息

作者简介:

通讯作者:
吴畏，男，博士，主任医师，研究方向为围术期重要脏器功能保护、缺氧缺血所致脏器损伤，Email：wuweizj@163.com

中图分类号: R617, R575.7
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出版历程
- 收稿日期: 2022-02-08
- 网络出版日期: 2022-07-14
- 刊出日期: 2022-07-15

Research progress on the role of bile salts in ischemic-type biliary lesion after liver transplantation

Department of Anesthesiology and Pain, the General Hospital of Western Theater Command of Chinese People's Liberation Army, Chengdu 610083, China

More Information

Corresponding author: Wu Wei, Email: wuweizj@163.com

摘要

摘要: 缺血性胆道病变(ITBL)是由于肝动脉供血不足所导致的胆道受损，是影响肝移植受者长期生存和生活质量的主要因素之一，其发病与冷、热缺血，急、慢性排斥反应，巨细胞病毒感染，胆汁作用等多种因素有关。ITBL的发生是一个多因素、多环节的复杂过程，其治疗手段匮乏，相当一部分患者需要再次肝移植。ITBL已成为阻碍肝移植疗效进一步提高的最主要因素之一，因此加强预防以及寻找更多有效的治疗途径显得尤为重要。近年来发现胆盐的毒性损伤在ITBL中起着中心环节的作用，胆汁成分的主动调节、胆汁酸相关受体表达的调控、胆汁酸相关信号通路的阻断或激活，可能在ITBL的预防和治疗中具备较大的潜力。本文综述了胆盐细胞毒性以及碳酸氢盐伞在肝移植术后ITBL发生、发展中的作用机制，旨在为未来ITBL的诊断和治疗提供参考。
- 胆盐 /
- 磷脂 /
- 肝移植 /
- 缺血性胆道病变(ITBL) /
- 缺血-再灌注损伤 /
- 碳酸氢盐伞 /
- 阴离子交换蛋白2 /
- 可溶性腺苷酸环化酶(sAC)
Abstract: Ischemic-type biliary lesion (ITBL) refers to biliary tract injury caused by insufficient blood supply of hepatic artery, which is one of the main factors affecting the long-term survival and quality of life of liver transplant recipients. The incidence of ITBL is associated with cold and warm ischemia, acute and chronic rejection, cytomegalovirus infection and the bile effect, etc. The occurrence of ITBL is a complicated process involving with multiple factors and steps. The therapeutic option of ITBL is extremely limited. A large proportion of ITBL patients should undergo repeated liver transplantation. ITBL has become one of the most critical factors preventing further advancement of liver transplantation. Hence, it is of significance to strengthen prevention and explore more effective modalities. Recent studies have found that toxic injury of bile salts plays a central role in ITBL. Active regulation of bile components, regulation of bile acid-related receptor expression and blockage or activation of bile acid-related signaling pathways probably have potentials in the prevention and treatment of ITBL. In this article, the cytotoxicity of bile salts and the mechanism of bicarbonate umbrella in the incidence and progression of ITBL after liver transplantation were reviewed, aiming to provide reference for the diagnosis and treatment of ITBL.
- Bile salt /
- Phospholipid /
- Liver transplantation /
- Ischemic-type biliary lesion (ITBL) /
- Ischemia-reperfusion injury /
- Bicarbonate umbrella /
- Anion exchanger 2 /
- Soluble adenylyl cyclase (sAC)

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图 1 胆管细胞分泌胆汁碳酸氢盐的主要机制

注：ATP为三磷酸腺苷；cAMP为环磷酸腺苷；CFTR为囊性纤维化跨膜电导调节因子；CHMR3为胆碱能M3受体；IP3为三磷酸肌醇；IP3R为三磷酸肌醇受体；PKA为蛋白激酶A；PKC为蛋白激酶C；ER为内质网；AE2为阴离子交换蛋白2。

Figure 1. The main mechanism of bile bicarbonate secretion by bile duct cells

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图 2 在AE2下调情况下sAC参与胆管细胞损伤的机制假说

注：BAs为疏水性胆盐；JNK为c-JNK氨基末端激酶；MOMP为线粒体外膜通透化；cAMP为环磷酸腺苷；CFTR为囊性纤维化跨膜电导调节因子；Bax为B淋巴细胞瘤-2相关X蛋白。

Figure 2. Mechanistic hypothesis of the involvement of sAC in cholangiocyte injury in the context of AE2 downregulation

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