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使用全氟碳化合物进行肝移植保存可改善大鼠心脏死亡后供肝移植的模拟结局。

Liver graft preservation using perfluorocarbon improves the outcomes of simulated donation after cardiac death liver transplantation in rats.

机构信息

Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Departments of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.

Transplant Institute, Allegheny General Hospital, Pittsburgh, PA.

出版信息

Liver Transpl. 2017 Sep;23(9):1171-1185. doi: 10.1002/lt.24806.

Abstract

The outcomes of liver transplantation (LT) from donation after cardiac death (DCD) donors remain poor due to severe warm ischemia injury. Perfluorocarbon (PFC) is a novel compound with high oxygen carrying capacity. In the present study, a rat model simulating DCD LT was used, and the impact of improved graft oxygenation provided by PFC addition on liver ischemia/reperfusion injury (IRI) and survival after DCD LT was investigated. Orthotopic liver transplants were performed in male Lewis rats, using DCD liver grafts preserved with cold University of Wisconsin (UW) solution in the control group and preserved with cold oxygenated UW solution with addition of 20% PFC in the PFC group. For experiment I, in a 30-minute donor warm ischemia model, postoperative graft injury was analyzed at 3 and 6 hours after transplantation. For experiment II, in a 50-minute donor warm ischemia model, the postoperative survival was assessed. For experiment I, the levels of serum aspartate aminotransferase, alanine aminotransferase, hyaluronic acid, malondialdehyde, and several inflammatory cytokines were significantly lower in the PFC group. The hepatic expression levels of tumor necrosis factor α and interleukin 6 were significantly lower, and the expression level of heme oxygenase 1 was significantly higher in the PFC group. Histological analysis showed significantly less necrosis and apoptosis in the PFC group. Sinusoidal endothelial cells and microvilli of the bile canaliculi were well preserved in the PFC group. For experiment II, the postoperative survival rate was significantly improved in the PFC group. In conclusion, graft preservation with PFC attenuated liver IRI and improved postoperative survival. This graft preservation protocol might be a new therapeutic option to improve the outcomes of DCD LT. Liver Transplantation 23 1171-1185 2017 AASLD.

摘要

肝移植(LT)供体来源于心脏死亡后捐献(DCD)的患者,由于严重的热缺血损伤,其预后仍然较差。全氟化碳(PFC)是一种新型化合物,具有较高的携氧能力。本研究采用模拟 DCD LT 的大鼠模型,研究 PFC 对供肝氧合的改善对 DCD LT 后肝缺血再灌注损伤(IRI)和存活的影响。在雄性 Lewis 大鼠中进行原位肝移植,对照组使用冷 UW 溶液保存 DCD 供肝,实验组使用含 20%PFC 的冷氧合 UW 溶液保存。在 30 分钟供体热缺血模型中,在移植后 3 小时和 6 小时分析术后移植物损伤。在 50 分钟供体热缺血模型中,评估术后存活率。在实验 I 中,PFC 组血清天冬氨酸转氨酶、丙氨酸转氨酶、透明质酸、丙二醛和几种炎症细胞因子水平显著降低。PFC 组肿瘤坏死因子α和白细胞介素 6 的肝表达水平显著降低,血红素加氧酶 1 的表达水平显著升高。组织学分析显示 PFC 组坏死和凋亡明显减少。PFC 组肝窦内皮细胞和胆小管微绒毛保存良好。在实验 II 中,PFC 组的术后存活率显著提高。总之,PFC 保存移植物减轻了肝 IRI 并改善了术后存活率。这种供体保存方案可能是改善 DCD LT 结果的新治疗选择。肝移植 23 1171-1185 2017 AASLD。

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