Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Nanjing, China.
J Surg Res. 2013 Jan;179(1):e245-53. doi: 10.1016/j.jss.2012.02.007. Epub 2012 Mar 28.
The size of the liver donor graft is a major concern in living donor liver transplantation. Rapid regeneration is essential for the survival of these grafts. The purpose of this study was to investigate the effect of remote ischemic preconditioning (RIPC) on liver regeneration in a rat small-for-size liver transplantation model.
We established rat models of small-for-size liver transplantation (30%) in the presence or absence (control) of remote ischemic preconditioning. We observed liver mass regeneration, serum alanine aminotransferase, hepatic pathologic alterations, flow cytometry, and Ki-67 antigen immunohistochemistry. In addition, using Western blotting and reverse-transcriptase-polymerase chain reaction, we assessed the activation of cell cycle progression as well as tumor necrosis factor-α and interleukin-6 expression.
Compared with the control group, serum alanine aminotransferase activity was significantly lower and histopathology changes were significantly attenuated in the RIPC group. Remote ischemic preconditioning induced a high level of interleukin-6 mRNA in small grafts, but suppressed the expression of tumor necrosis factor-α. The proliferation index, indicated by the S-phase and G2/M-phase ratio [(S+G2/M)/(G0/G1+S+G2/M)], was significantly increased in the RIPC group at 24 h (58.25% ± 0.506% versus 53.405% ± 1.25%; P = .007). Meanwhile, cell cycle progression and regeneration (Ki-67) were initiated early in liver grafts treated with RIPC.
These results suggest that RIPC can protect liver cells against ischemia reperfusion injury in the small grafts and enhance liver regeneration. Interleukin-6 may be a critical mediator in the stimulatory effect on liver cell regeneration, which may make RIPC valuable as a hepatoprotective modality.
供肝体积大小是活体肝移植的主要关注点。快速再生对于这些移植物的存活至关重要。本研究旨在探讨远程缺血预处理（RIPC）对大鼠小体积肝移植模型中肝再生的影响。
我们在存在（RIPC 组）或不存在（对照组）远程缺血预处理的情况下建立了大鼠小体积肝移植（30%）模型。我们观察了肝质量再生、血清丙氨酸氨基转移酶、肝组织病理学改变、流式细胞术和 Ki-67 抗原免疫组织化学。此外，我们通过 Western blot 和逆转录-聚合酶链反应评估了细胞周期进程的激活以及肿瘤坏死因子-α和白细胞介素-6 的表达。
与对照组相比，RIPC 组血清丙氨酸氨基转移酶活性明显降低，组织病理学改变明显减轻。RIPC 在小移植物中诱导高水平的白细胞介素-6 mRNA，但抑制肿瘤坏死因子-α的表达。增殖指数，即 S 期和 G2/M 期比例[(S+G2/M)/(G0/G1+S+G2/M)]，在 RIPC 组 24 小时时显著增加（58.25%±0.506%比 53.405%±1.25%；P=0.007）。同时，RIPC 处理的肝移植物中细胞周期进程和再生（Ki-67）较早开始。
这些结果表明，RIPC 可以保护小移植物中的肝细胞免受缺血再灌注损伤，并增强肝再生。白细胞介素-6 可能是刺激肝实质细胞再生的关键介质，这使得 RIPC 作为一种肝保护方式具有重要价值。
