Department of Hepatobiliary Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming, China.
Scand J Gastroenterol. 2023 Jul;58(7):771-781. doi: 10.1080/00365521.2023.2175180. Epub 2023 Feb 14.
Conventional hepatic artery and portal vein clamping strategies can prevent blood loss and ischemia-reperfusion liver injury, and such preventative measures are the key to successful liver surgery. However, ischemic-induced damage to cholangiocytes is rarely considered. Here, we aimed to investigate the effect of different hepatic inflow interruption methods on bile duct injury.
Forty rats were randomly grouped as sham, Pringle maneuver (PM) and hepatic arterial blood flow open (HAFO) groups. We evaluated liver histology and function in liver sections, and biliary histology, cholangiocyte apoptosis and proliferation, cytokine production, and bile composition. RNA sequencing is performed to explore possible molecular mechanisms. The Blood-biliary barrier permeability and tight junctions were analyzed by HRP injection, immunofluorescence staining and analysis of ZO-1 expression by immunoblotting.
HAFO significantly attenuated ischemia-induced liver injury and decreased ALT, ALP, TBIL, and DBIL levels in serum. The histopathological observations showed that bile duct injury in the PM group was more serious than that in the HAFO group. The numbers of apoptotic biliary epithelial cells in HAFO-treated rat bile ducta were lower than those in the PM group. RNA-seq showed that tight junctions may be related to the mechanism underlying the protective effect of HAFO, as shown by the reduced HRP levels and increased ZO-1 and claudin-1/3 expression in the HAFO group compared to the PM group.
Compared with PM, HAFO alleviated the ischemic injury to the biliary system, which was characterized by decreased biliary epithelial cell apoptosis, reduced inflammatory responses and decreased blood-biliary-barrier permeability.
传统的肝动脉和门静脉阻断策略可以预防出血和缺血再灌注肝损伤,这些预防措施是成功进行肝手术的关键。然而,很少考虑到缺血对胆管细胞的损伤。在这里,我们旨在研究不同肝血流阻断方法对胆管损伤的影响。
40 只大鼠随机分为假手术组、Pringle 手法(PM)组和肝动脉血流开放(HAFO)组。我们评估了肝组织学和功能、胆管组织学、胆管细胞凋亡和增殖、细胞因子产生和胆汁成分。进行 RNA 测序以探索可能的分子机制。通过 HRP 注射、免疫荧光染色和免疫印迹分析 ZO-1 表达来分析血-胆屏障通透性和紧密连接。
HAFO 显著减轻了缺血引起的肝损伤,并降低了血清中 ALT、ALP、TBIL 和 DBIL 的水平。组织病理学观察表明,PM 组的胆管损伤比 HAFO 组更严重。HAFO 处理的大鼠胆管中凋亡的胆管上皮细胞数量低于 PM 组。RNA-seq 显示,紧密连接可能与 HAFO 的保护作用机制有关,HAFO 组的 HRP 水平降低,ZO-1 和 claudin-1/3 表达增加,与 PM 组相比。
与 PM 相比,HAFO 减轻了胆管系统的缺血性损伤,其特征是胆管上皮细胞凋亡减少、炎症反应减轻和血-胆屏障通透性降低。