The conditioning effect of ex vivo normothermic perfusion in an experimental kidney model

The conditioning effect of ex vivo normothermic perfusion in an experimental kidney model
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DOI:
10.1016/j.jss.2012.08.001
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发表时间:
2013-06-01
影响因子:
2.2
通讯作者:
Nicholson, Michael L.
Nicholson, Michael L.
中科院分区:
医学3区
文献类型:
--
作者:
Hosgood, Sarah A.;Patel, Meeta;Nicholson, Michael L.

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背景:短时间的离体恒温灌注(NP)可用于改善热、冷缺血后肾脏的状况。然而,这种有益作用的机制尚未确定。材料和方法:在热缺血损伤10 min后取出猪肾脏,用静态冷库(CS)保存24 h(对照组),或用冷库保存23 h,然后用去白细胞的自体血液(NP)在38℃下NP 1 h。保存后,两组肾脏进行3 h的离体再灌注以评估损伤(n = 6)。结果:与对照组相比,再灌注时NP组肾脏肾内阻力水平显著降低(NP为2.28 +/- 1.1,对照组为3.86 +/- 1.2 mm Hg/mL/h, P = 0.040),维持酸碱稳态(P = 0.080),耗氧量更高(NP为42.6 +/- 19.5,对照组为20.8 +/- 5.7 mL/min/g, P = 0.026),肾小管损伤减少(P = 0.008)。炎症因子(白细胞介素[IL]-1b、IL-8或肿瘤坏死因子-a; P < 0.05)水平或肾功能(肌酐清除率NP < 2.6 +/- 1.3 vs >对照组< 3.0 +/- 1.5 mL/min/100 g; P = 0.070)均无显著差异。再灌注后,NP组IL-6水平明显升高(P = 0.016)。NP 1 h后热休克蛋白70表达上调,再灌注时表达增加,显著高于对照组(P = 0.045)。结论:与静态冷藏肾脏相比,短时间NP处理肾脏代谢功能改善,肾小管损伤减轻。热休克蛋白70和IL-6的表达增加表明NP可能上调了肾脏的调节机制。(C) 2013爱思唯尔公司版权所有。
Background: A short period of isolated normothermic perfusion (NP) can be used to improve the condition of the kidney after periods of warm and cold ischemic injury. However, the mechanisms underlying this beneficial effect have not been determined.Materials and methods: Porcine kidneys were retrieved after 10 min of warm ischemic injury and stored by either static cold storage (CS) for 24 h (control) or CS for 23 h followed by 1 h of NP at 38 degrees C with leukocyte-depleted autologous blood (NP). After preservation, kidneys in both groups underwent 3 h of ex vivo reperfusion to assess the injury (n = 6).Results: NP kidneys had significantly lower levels of intrarenal resistance (NP 2.28 +/- 1.1 versus control 3.86 +/- 1.2 mm Hg/mL/h; P = 0.040), maintained their acid base homeostasis (P = 0.080), and had higher levels of oxygen consumption (NP 42.6 +/- 19.5 versus control 20.8 +/- 5.7 mL/min/g; P = 0.026) and reduced tubular injury (P = 0.008) compared with kidneys in the control group during reperfusion. There were no significant differences in the levels of inflammatory cytokines (interleukin [IL]-1b, IL-8, or tumor necrosis factor-a; P > 0.05) or in renal function (creatinine clearance NP 2.6 +/- 1.3 versus control 3.0 +/- 1.5 mL/min/100 g; P = 0.070). However, levels of IL-6 were significantly raised in the NP group after reperfusion (P = 0.016). Levels of heat shock protein 70 were upregulated after 1 h of NP and expression increased during reperfusion to a significantly higher level than in the control group (P = 0.045).Conclusion: Kidneys undergoing a short period of NP had improved metabolic function and less tubular injury compared with static cold-stored kidneys. The increased expression of heat shock protein 70 and IL-6 suggests that NP may upregulate mechanisms that condition the kidney. (C) 2013 Elsevier Inc. All rights reserved.