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远隔缺血预处理对肝缺血再灌注损伤晚期微循环变化的调节作用。

Modulation of microcirculatory changes in the late phase of hepatic ischaemia-reperfusion injury by remote ischaemic preconditioning.

机构信息

Hepatopancreatobiliary and Liver Transplant Unit, Department of Surgery, Royal Free Hospital, University College London, London, UK.

出版信息

HPB (Oxford). 2012 Feb;14(2):87-97. doi: 10.1111/j.1477-2574.2011.00407.x. Epub 2011 Nov 27.

DOI:10.1111/j.1477-2574.2011.00407.x
PMID:22221569
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3277050/
Abstract

BACKGROUND

Remote ischaemic preconditioning (RIPC) is a novel method of protecting the liver from ischaemia-reperfusion (I-R) injury. Protective effects in the early phase (4-6 h) have been demonstrated, but no studies have focused on the late phase (24 h) of hepatic I-R. This study analysed events in the late phase of I-R following RIPC and focused on the microcirculation, inflammatory cascade and the role of cytokine-induced neutrophil chemoattractant-1 (CINC-1).

METHODS

A standard animal model was used. Remote preconditioning prior to I-R was induced by intermittent limb ischaemia. Ischaemia was induced in the left and median lobes of the liver (70%). The animals were recovered after 45 min of liver ischaemia. At 24 h, the animals were re-evaluated under anaesthesia. Hepatic microcirculation, sinusoidal leukocyte adherence and hepatocellular death were assessed by intravital microscopy, hepatocellular injury by standard biochemistry and serum CINC-1 by enzyme-linked immunosorbent assay (ELISA).

RESULTS

At 24 h post I-R, RIPC was found to have improved sinusoidal flow by increasing the sinusoidal diameter. There was no effect of preconditioning on the velocity of red blood cells, by contrast with the early phase of hepatic I-R. Remote ischaemic preconditioning significantly reduced hepatocellular injury, neutrophil-induced endothelial injury and serum CINC-1 levels.

CONCLUSIONS

Remote ischaemic preconditioning is amenable to translation into clinical practice and may improve outcomes in liver resection surgery and transplantation.

摘要

背景

远程缺血预处理(RIPC)是一种保护肝脏免受缺血再灌注(I-R)损伤的新方法。已证明其在早期(4-6 小时)具有保护作用,但尚无研究关注 I-R 的晚期(24 小时)。本研究分析了 RIPC 后 I-R 的晚期事件,并重点关注了微循环、炎症级联反应以及细胞因子诱导的中性粒细胞趋化因子-1(CINC-1)的作用。

方法

使用标准动物模型。I-R 前的远程预处理通过间歇性肢体缺血来诱导。肝脏的左叶和中叶(70%)发生缺血。缺血 45 分钟后,动物恢复。24 小时后,动物在麻醉下重新评估。通过活体显微镜评估肝微循环、窦状隙白细胞黏附和肝细胞死亡,通过标准生化评估肝细胞损伤,通过酶联免疫吸附试验(ELISA)评估血清 CINC-1。

结果

在 I-R 后 24 小时,发现 RIPC 通过增加窦状隙直径来改善窦状隙血流。与肝脏 I-R 的早期阶段相比,预处理对红细胞速度没有影响。远程缺血预处理显著降低了肝细胞损伤、中性粒细胞诱导的内皮损伤和血清 CINC-1 水平。

结论

远程缺血预处理易于转化为临床实践,并可能改善肝切除术和移植术的结果。

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本文引用的文献

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Effect of remote ischemic preconditioning on hepatic microcirculation and function in a rat model of hepatic ischemia reperfusion injury.远程缺血预处理对肝缺血再灌注损伤大鼠模型肝微循环和功能的影响。
HPB (Oxford). 2009 Mar;11(2):108-17. doi: 10.1111/j.1477-2574.2009.00006.x.
2
Glycine reduces hepatic warm ischaemia-reperfusion injury by suppressing inflammatory reactions in rats.甘氨酸通过抑制大鼠的炎症反应减轻肝脏热缺血再灌注损伤。
Liver Int. 2007 Nov;27(9):1249-54. doi: 10.1111/j.1478-3231.2007.01564.x.
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Effects of ischemic liver preconditioning on hepatic ischemia/reperfusion injury in the rat.缺血性肝预处理对大鼠肝脏缺血/再灌注损伤的影响。
Transplant Proc. 2007 Mar;39(2):361-4. doi: 10.1016/j.transproceed.2007.01.011.
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Remote ischaemic preconditioning of the hind limb reduces experimental liver warm ischaemia-reperfusion injury.后肢远程缺血预处理可减轻实验性肝脏热缺血再灌注损伤。
Br J Surg. 2006 Jun;93(6):762-8. doi: 10.1002/bjs.5331.
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Ischemic preconditioning of cadaver donor livers protects allografts following transplantation.尸体供肝的缺血预处理可保护移植后的同种异体移植物。
Transplantation. 2006 Jan 27;81(2):169-74. doi: 10.1097/01.tp.0000188640.05459.37.
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Ischemic preconditioning improves energy state and transplantation survival in obese Zucker rat livers.缺血预处理可改善肥胖 Zucker 大鼠肝脏的能量状态及移植存活率。
Anesth Analg. 2005 Dec;101(6):1577-1583. doi: 10.1213/01.ANE.0000184897.53609.2A.
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Ischemic preconditioning and liver tolerance to warm or cold ischemia: experimental studies in large animals.缺血预处理与肝脏对热缺血或冷缺血的耐受性:大型动物实验研究
Transplantation. 2005 May 27;79(10):1393-400. doi: 10.1097/01.tp.0000164146.21136.0b.
8
Mild hypothermia provides significant protection against ischemia/reperfusion injury in livers of obese and lean rats.轻度低温对肥胖和瘦大鼠肝脏的缺血/再灌注损伤具有显著的保护作用。
Ann Surg. 2005 Mar;241(3):470-6. doi: 10.1097/01.sla.0000154259.73060.f1.
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Remote preconditioning reduces ischemic injury in the explanted heart by a KATP channel-dependent mechanism.远程预处理通过一种依赖于ATP敏感性钾通道的机制减少离体心脏的缺血性损伤。
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Am J Physiol Heart Circ Physiol. 2005 Feb;288(2):H559-67. doi: 10.1152/ajpheart.00845.2004. Epub 2004 Sep 30.