Cheung Ernest, Nikfarjam Mehrdad, Jackett Louise, Bolton Damien M, Ischia Joseph, Patel Oneel
Department of Surgery, The University of Melbourne, Victoria, Australia.
Department of Anatomical Pathology, Austin Health, Heidelberg, Victoria, Australia.
J Clin Exp Hepatol. 2020 May-Jun;10(3):228-235. doi: 10.1016/j.jceh.2019.07.006. Epub 2019 Jul 24.
Ischaemia-reperfusion injury (IRI) is a major obstacle during liver transplantation and resection surgeries for cancer, with a need for effective and safe drugs to reduce IRI. Zinc preconditioning has been shown to protect against liver IRI in a partial (70%) ischaemia model. However, its efficacy against a clinically relevant Pringle manoeuvre that results in global liver ischaemia (100%) is unknown.
The aim of this study was to test the efficacy of zinc preconditioning in a rat model of global liver ischaemia.
Rats were preconditioned via subcutaneous injection of 10 mg/kg of ZnCl, 24 h and 4 h before ischaemia. Total liver ischaemia (100%) was induced by placing a clamp across the portal triad for 30 min. Liver injury was assessed by serum alanine transaminase (ALT) and aspartate transaminase (AST) levels in blood taken before ischaemia (baseline) and at 1, 2, 4, 24, 48, 72, 96 and 120 hours after ischaemia. Animals were culled after 7 days, and the harvested livers were histologically analysed.
On a two-way repeated-measures analysis of variance, there was a statistically significant (p = 0.025) difference in the mean ALT levels between saline- and ZnCl-treated groups. Specifically at 24 h after ischaemia, the ALT (341 ± 99 U/L) and AST (606 ± 78 U/L) in the zinc-treated group were significantly less than the ALT (2863 ± 828 U/L) and AST (3591 ± 948 U/L) values in the saline-treated group. Zinc significantly reduced neutrophil infiltration and necrosis compared with the saline control.
Zinc preconditioning reduces the overall hepatocellular damage from IRI. These results lay the foundation to assess the benefit of zinc preconditioning for clinical applications.
缺血再灌注损伤（IRI）是肝移植和癌症切除手术中的主要障碍，需要有效且安全的药物来减轻IRI。锌预处理已被证明在部分（70%）缺血模型中可预防肝脏IRI。然而，其对导致全肝缺血（100%）的临床相关Pringle手法的疗效尚不清楚。
本研究的目的是在大鼠全肝缺血模型中测试锌预处理的疗效。
在缺血前24小时和4小时，通过皮下注射10mg/kg的ZnCl对大鼠进行预处理。通过在门静脉三联处放置夹子30分钟诱导全肝缺血（100%）。在缺血前（基线）以及缺血后1、2、4、24、48、72、96和120小时采集血液，通过血清丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）水平评估肝损伤。7天后对动物实施安乐死，并对收获的肝脏进行组织学分析。
在双向重复测量方差分析中，盐水处理组和ZnCl处理组之间的平均ALT水平存在统计学显著差异（p = 0.025）。具体而言，在缺血后24小时，锌处理组的ALT（341±99 U/L）和AST（606±78 U/L）显著低于盐水处理组的ALT（2863±828 U/L）和AST（3591±948 U/L）值。与盐水对照组相比，锌显著减少了中性粒细胞浸润和坏死。
锌预处理可减轻IRI对肝细胞的总体损伤。这些结果为评估锌预处理在临床应用中的益处奠定了基础。
