持续性胰胆反流（PBR）与胆道恶性肿瘤的高风险相关。本研究旨在评估PBR在胆道疾病中的比例以及PBR促进胆管癌进展的机制。共有227名原发性胆道疾病患者连续参与本研究。分析收集的胆汁中的淀粉酶水平。分析了高淀粉酶胆汁对胆管上皮细胞和胆管癌细胞进展影响的机制。研究白细胞介素8(IL-8)的来源及其对胆管癌细胞生物学功能的影响。227例患者中148例胆汁淀粉酶水平高于血清淀粉酶上限135 IU/L。 PBR 与患者队列中的性别、发热和血清 γ-谷氨酰转移酶 (GGT) 水平显着相关。高淀粉酶胆汁诱导DNA损伤和胆囊粘膜转录水平的遗传差异，促进胆管癌细胞（HUCCT1和QBC939细胞）的增殖和迁移。高淀粉酶胆汁中许多细胞因子的浓度增加。 IL-8 主要由巨噬细胞通过丝裂原激活蛋白激酶途径分泌，部分由胆管上皮细胞分泌。 IL-8通过调节上皮间质转化相关蛋白的表达并激活磷脂酰肌醇3激酶/核因子κ-B通路来促进HUCCT1和QBC939细胞的进展。PBR是胆道疾病的主要原因之一。高淀粉酶胆汁刺激的巨噬细胞或胆管上皮细胞分泌的 IL-8 可促进胆管癌进展。版权所有 © 2024。由 Elsevier Inc. 出版。

Persistent pancreaticobiliary reflux (PBR) is associated with a high risk of biliary malignancy. This study aimed to evaluate the proportion of PBR in biliary tract diseases and mechanisms by which PBR promoted cholangiocarcinoma progression.Overall 227 consecutive patients with primary biliary tract disease participated in this study. The amylase levels in the collected bile were analyzed. The mechanisms underlying the effect of high-amylase bile on bile duct epithelial and cholangiocarcinoma cells progression were analyzed. The source of interleukin-8 (IL-8) and its effects on the biological functions of cholangiocarcinoma cells were investigated.The bile amylase levels in 148 of 227 patients were higher than the upper serum amylase limit of 135 IU/L. PBR was significantly correlated with sex, pyrexia, and serum gamma-glutamyl transferase (GGT) levels in the patient cohort. High-amylase bile-induced DNA damage and genetic differences in the transcript levels of the gallbladder mucosa and facilitated the proliferation and migration of bile duct cancer cells (HUCCT1 and QBC939 cells). The concentration of many cytokines increased in high-amylase bile. IL-8 is secreted primarily by macrophages via the mitogen-activated protein kinase pathway and partially by bile duct epithelial cells. IL-8 promotes the progression of HUCCT1 and QBC939 cells by regulating the expression of epithelial-mesenchymal transition-associated proteins and activating the phosphatidylinositol 3-kinase/nuclear factor kappa-B pathway.PBR is one of the primary causes of biliary disease. IL-8 secreted by macrophages or bile duct epithelial cells stimulated by high-amylase bile promotes cholangiocarcinoma progression.Copyright © 2024. Published by Elsevier Inc.