1H-NMR-based metabolic signatures of mild and severe ischemia/reperfusion injury in rat kidney transplants
1H-NMR-based metabolic signatures of mild and severe ischemia/reperfusion injury in rat kidney transplants
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DOI：
10.1111/j.1523-1755.2005.00181.x
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发表时间：
2005-03-01
影响因子：
19.6
通讯作者：
Niemann, CU
中科院分区：
文献类型：
--
作者：
Serkova, N;Fuller, TF;Niemann, CU
背景。严重的缺血再灌注（IR）损伤是移植物功能延迟的危险因素。延迟移植物功能仍然难以预测，目前主要依赖于血清肌酐（SCr）、尿量，偶尔也依赖于移植物活检。利用H-1-NMR（核磁共振波谱）代谢组学在血液和肾脏组织中建立ir特异性代谢标志物。将这些标记物与SCr和移植物组织进行比较。雄性Lewis大鼠用于肾移植。2个冷缺血（CI）组（24小时和42小时）和2个移植组[CI后24小时（TX24）和42小时（TX42）]与对照组进行比较。采集全血和肾组织作进一步分析。移植后24小时SCr水平分别为1.6 +/- 0.12 mg/dL （TX24）和2.1 +/- 0.5 mg/dL (TX42), P = 0.05。组织学显示TX24组为轻度损伤，TX42组为重度损伤。在肾组织中发现多不饱和脂肪酸（PUFA）水平显著降低，尿囊素（氧化应激的标志）水平升高。在血液中，三甲胺- n -氧化物（TMAO），肾髓质损伤的标志，尿囊素显著升高。对照组和Cl组尿囊素水平均较低。再灌注后血药浓度显著升高（对照组0.02 +/- 0.03 μ mol/mL, TX24 1.13 +/- 0.22, TX42 1.89 +/- 0.38, P < 0.001），并与冷缺血时间（r = 0.96）和TMAO （r = 0.94）相关。轻度和重度IR组的H-1-NMR代谢谱显示出与移植物组织学一致的显著变化，而SCr则没有。
Background. Severe ischemia/reperfusion (IR) injury is a risk factor for delayed graft function. Delayed graft function remains difficult to predict, and it currently relies primarily on serum creatinine (SCr), urine output, and occasionally on graft biopsy. H-1-NMR (nuclear magnetic resonance spectroscopy) based metabolomics was used to establish IR-specific metabolic markers in both blood and kidney tissue. These markers were compared to SCr and graft histology.Methods. Male Lewis rats were used for kidney transplantation. Two cold ischernia (CI) groups (24- and 42-hour) and two transplantation groups [after 24 (TX24) and after 42 hours (TX42) of CI] were compared to a control group. Whole blood and kidney tissue were collected for further analysis.Results. SCr levels taken 24 hours after transplantation were 1.6 +/- 0.12 mg/dL (TX24) and 2.1 +/- 0.5 mg/dL (TX42), (P = n.s.). Histology samples revealed mild injury in the TX24 group and severe injury in the TX42 group. A significantly decreased level of polyunsaturated fatty acids (PUFA) and elevated levels of allantoin, a marker of oxidative stress, was found in the renal tissue. In the blood, both trimethylamine-N-oxide (TMAO), a marker of renal medullary injury, and allantoin were significantly increased. Allantoin levels were low in both the control and Cl groups. Levels were significantly increased after reperfusion (control 0.02 +/- 0.03 mumol/mL, TX24 1.13 +/- 0.22, and TX42 1.89 +/- 0.38, P < 0.001), and correlated with cold ischernia time (r = 0.96) and TMAO (r = 0.94).Conclusion. The H-1-NMR metabolic profiles of both the mild and severe IR groups revealed significant changes consistent with graft histology, while the SCr did not.