Remote ischemic preconditioning promotes early liver cell proliferation in a rat model of small-for-size liver transplantation.

Remote ischemic preconditioning promotes early liver cell proliferation in a rat model of small-for-size liver transplantation.
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远程缺血预处理促进小型肝移植大鼠模型的早期肝细胞增殖。

DOI:
10.1016/j.jss.2012.02.007
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发表时间:
2013
影响因子:
2.2
通讯作者:
Li, Xiangcheng
Li, Xiangcheng
中科院分区:
医学3区
文献类型:
--
作者:
Chen, Qi;Zhang, Bin;Tang, Jincao;Li, Xiangcheng

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供体肝移植的大小是活体肝移植的一个主要问题。快速再生对于这些移植物的存活至关重要。本研究采用大鼠小体积肝移植模型,观察远程缺血预处理(remote ischemic preconditioning,RIPC)对肝再生的影响。观察肝组织再生、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抗原免疫组化。此外,采用Western blotting和RT-PCR方法检测RIPC对细胞周期进程的激活以及肿瘤坏死因子-α(TNF-α)和白细胞介素-6(IL-6)的表达。结果: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。远程缺血预处理可诱导小移植物中IL-6 mRNA表达升高,但抑制肿瘤坏死因子-α的表达。RIPC组24 h时的增殖指数(S期和G2/M期比值[(S+G2/M)/(G 0/G1+S+G2/M)])显著增加(58.25% ± 0.506% vs 53.405% ± 1.25%; P = 0.007)。同时,RIPC处理的肝移植物细胞周期进程和再生(Ki-67)启动较早。结论RIPC可保护小移植肝细胞免受缺血再灌注损伤,促进肝再生。白细胞介素-6可能是一个关键的介质,在刺激作用对肝细胞再生,这可能使RIPC作为一个有价值的保肝方式。
BACKGROUNDThe 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.METHODSWe 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.RESULTSCompared 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.CONCLUSIONSThese 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.
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DOI: 10.1053/jhep.2003.50009
发表时间: 2003-01-01
期刊: HEPATOLOGY
影响因子: 13.5
作者:
Teoh, N;Leclercq, I;Farrell, G
通讯作者: Farrell, G
DOI: 10.1002/hep.510300215
发表时间: 1999-08
期刊: Hepatology
影响因子: 13.5
作者:
M. Selzner;Carlos A. Camargo;P. Clavien
通讯作者: M. Selzner;Carlos A. Camargo;P. Clavien
DOI: 10.1002/bjs.5331
发表时间: 2006-06-01
影响因子: 9.6
作者:
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通讯作者: Davidson, B. R.
DOI: 10.1161/01.cir.74.5.1124
发表时间: 1986-11-01
期刊: CIRCULATION
影响因子: 37.8
作者:
MURRY, CE;JENNINGS, RB;REIMER, KA
通讯作者: REIMER, KA