Ex vivo application of carbon monoxide in UW solution prevents transplant-induced renal ischemia/reperfusion injury in pigs.
Ex vivo application of carbon monoxide in UW solution prevents transplant-induced renal ischemia/reperfusion injury in pigs.
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DOI：
10.1111/j.1600-6143.2010.03040.x
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发表时间：
2010-04
期刊：
影响因子：
--
通讯作者：
Murase N
中科院分区：
文献类型：
--
作者：
Yoshida J;Ozaki KS;Nalesnik MA;Ueki S;Castillo-Rama M;Faleo G;Ezzelarab M;Nakao A;Ekser B;Echeverri GJ;Ross MA;Stolz DB;Murase N
I/R损伤是影响肾移植成功的主要因素。一氧化碳（CO）是一种内源性气体调节分子，外源性低浓度CO可提供有效的细胞保护作用。本研究评价了在猪KTx模型中CO暴露于切除的肾移植物以抑制I/R损伤的功效。将猪肾在对照UW或补充CO的UW（CO-UW）中储存48小时，并在14天的随访研究中自体移植。在对照UW组中，动物存活率为80%（4/5），血清肌酐峰值水平为12.0±5.1 mg/dl。CO-UW显示出有效的保护作用，峰值肌酐水平降至6.9±1.4 mg/dl，100%（5/5）存活，无任何明显的不良事件或异常COHb值。对照移植物在14天时显示出显著的肾小管损伤、局灶性纤维化变化和大量浸润。CO-UW组的组织病理学改变明显减轻，TGF-β和p-Smad 3表达减少。移植物在CO-UW也表现出显着较低的早期mRNA水平的促炎细胞因子和较少的脂质过氧化。在猪KTx模型中，UW中的CO提供了针对肾I/R损伤的显著保护。因此，在冷藏期间将移植肾离体暴露于CO可能是减少I/R损伤的安全策略。
I/R injury is a major deleterious factor of successful kidney transplantation (KTx). Carbon monoxide (CO) is an endogenous gaseous regulatory molecule, and exogenously delivered CO in low concentrations provides potent cytoprotection. This study evaluated efficacies of CO exposure to excised kidney grafts to inhibit I/R injury in the pig KTx model. Porcine kidneys were stored for 48 hrs in control UW or UW supplemented with CO (CO-UW) and autotransplanted in a 14-day follow-up study. In the control UW group, animal survival was 80% (4/5) with peak serum creatinine levels of 12.0±5.1 mg/dl. CO-UW showed potent protection, and peak creatinine levels were reduced to 6.9±1.4 mg/dl with 100% (5/5) survival without any noticeable adverse event or abnormal COHb value. Control grafts at 14d showed significant tubular damages, focal fibrotic changes, and numerous infiltrates. The CO-UW group showed significantly less severe histopathological changes with less TGF-β and p-Smad3 expression. Grafts in CO-UW also showed significantly lower early mRNA levels for proinflammatory cytokines and less lipid peroxidation. CO in UW provides significant protection against renal I/R injury in the porcine KTx model. Ex vivo exposure of kidney grafts to CO during cold storage may therefore be a safe strategy to reduce I/R injury.
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影响因子：
4.6
作者：
Ikeda, Atsushi;Ueki, Shinya;Nakao, Atsunori;Tomiyama, Koji;Ross, Mark A.;Stolz, Donna B.;Geller, David A.;Murase, Noriko
通讯作者：
Murase, Noriko
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9.6
作者：
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Rigotti, P
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19.6
作者：
Liu, Fang;Wei, Chih-Chang;Chan, John S. D.
通讯作者：
Chan, John S. D.
影响因子：
2.2
作者：
Sipos, W;Duvigneau, C;Schmoll, F
通讯作者：
Schmoll, F