Second Department of Hepatobiliary Surgery, Zhujiang Hospital, State Key Laboratory of Organ Failure Research, Co-Innovation Center for Organ Failure Research, Southern Medical University, Guangzhou 510280, China.
Institute of Regenerative Medicine, Zhujiang Hospital, Guangdong Provincial Research Center for Artificial Organ and Tissue Engineering, Southern Medical University, Guangzhou 510280, China.
Biomed Res Int. 2016;2016:3518989. doi: 10.1155/2016/3518989. Epub 2016 Dec 21.
Models using large animals that are suitable for studying artificial liver support system (ALSS) are urgently needed. Presently available acute liver failure (ALF) models mainly involve pigs or dogs. Establishment of current surgical ALF models (hepatectomy/devascularization) requires either very good surgical skills or multistep processes-even multiple stages of surgery. Therefore, it is necessary to develop a simplified surgical method. Here we report a novel simplified surgical ALF model using cynomolgus monkeys. Six monkeys underwent portal-right renal venous shunt combined with common bile duct ligation and transection (PRRS + CBDLT). Postoperatively, the monkeys had progressively increased listlessness, loss of appetite, and obvious jaundice. Blood biochemistry levels (Amm, ALT, AST, TBiL, DBiL, ALP, LDH, CK, and Cr) and prothrombin time (PT) were significantly increased (all < 0.01) and albumin (ALB) was markedly reduced ( < 0.01) compared with baseline values. Histological examination of liver specimens on postoperative day 10 revealed cholestasis and inflammation. PRRS + CBDLT produced ALF that closely correlated with clinical situations. Compared with other surgical or drug ALF models, ours was simplified and animals were hemodynamically stable. This model could provide a good platform for further research on ALSS, especially regarding their detoxification functions.
目前可用的急性肝衰竭 (ALF) 模型主要涉及猪或狗。当前的手术性 ALF 模型（肝切除术/去血管化）需要非常好的手术技能或多步过程，甚至是多个手术阶段。因此，有必要开发一种简化的手术方法。在这里，我们报告了一种使用食蟹猴的新型简化手术性 ALF 模型。六只猴子接受了门静脉-右肾静脉分流术联合胆总管结扎和横断术（PRRS+CBDLT）。术后，猴子逐渐变得无精打采、食欲不振，并有明显的黄疸。与基线值相比，血液生化水平（Amm、ALT、AST、TBiL、DBiL、ALP、LDH、CK 和 Cr）和凝血酶原时间（PT）明显升高（均<0.01），白蛋白（ALB）明显降低（<0.01）。术后第 10 天肝组织学检查显示胆汁淤积和炎症。PRRS+CBDLT 引起的 ALF 与临床情况密切相关。与其他手术或药物性 ALF 模型相比，我们的模型更简单，动物血流动力学稳定。该模型可以为进一步研究人工肝支持系统（ALSS）提供良好的平台，特别是关于其解毒功能的研究。
