胆道损伤修复机制及新型治疗策略

Mechanisms of bile duct injury repair and novel therapeutic strategies

摘要:

胆道损伤可分为医源性和非医源性两大类，其中非医源性胆道损伤包括免疫性、感染性、血管性及缺血性、遗传性、特发性和肿瘤性损伤等。损伤后的胆管上皮会经历炎症修复、上皮再生修复、纤维修复等一系列紧密关联的病理过程，并通过自分泌和旁分泌机制与炎性细胞和间质细胞相互作用，协同调控修复过程，以维持胆道的结构与功能完整性。若缺乏有效干预，胆道损伤可导致胆汁漏、胆道狭窄，甚至进展为肝硬化，严重影响患者生活质量。目前胆道损伤的治疗方式不再局限于传统外科手术，还包括免疫调节、胆汁酸调节和肠道微生态调节等非手术治疗。随着医学技术的发展，基因治疗、干细胞/类器官技术以及经内镜逆行性胰胆管造影术/组织工程支架等新型治疗方式逐渐受到关注，并有望成为未来胆道损伤的有效治疗选择。本综述重点阐述胆道损伤的病因、修复过程中的病理机制，并梳理现有及潜在的治疗手段，为未来胆道损伤的研究和诊疗提供参考。

Abstract:

Bile duct injuries can be classified into iatrogenic and non-iatrogenic categories. Non-iatrogenic bile duct injuries include immune, infectious, vascular, ischemic, genetic, idiopathic, and neoplastic causes. After injury, the biliary epithelial cells undergo closely linked pathological processes, such as inflammatory repair, epithelial regeneration, and fibrous repair. These processes interact with inflammatory and stromal cells through autocrine and paracrine mechanisms, coordinating the repair process to maintain the structural and functional integrity of the bile ducts. In the absence of effective intervention, bile duct injuries can lead to bile leakage, biliary strictures, and even progress to cirrhosis, severely affecting the patient's quality of life. Currently, treating bile duct injuries is no longer limited to traditional surgical methods but also includes non-surgical treatments such as immune modulation, bile acid regulation, and gut microbiota adjustment. With the development of medical technology, novel treatments such as gene therapy, stem cell/organoid technology, and endoscopic retrograde cholangiopancreatography/tissue-engineered scaffolds are gaining attention and are expected to become effective treatment options for bile duct injuries in the future. This review focuses on the etiology and pathological mechanisms during the repair process of bile duct injuries and summarizes existing and potential treatment approaches, providing a reference for future research and clinical management of bile duct injuries.