Rahman N A, Mori K, Mizukami M, Suzuki T, Takahashi N, Ohyama C
Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
Transplant Proc. 2009 Nov;41(9):3603-10. doi: 10.1016/j.transproceed.2009.04.008.
In an acute kidney transplant rejection rat model, we demonstrated that manganese superoxide dismutase (MnSOD) activity was significantly reduced and MnSOD was nitrated by peroxynitrite (ONOO(-)), resulting in tissue injury. We examined whether tissue injury was reduced after external supplementation of recombinant human MnSOD in a rat renal ischemia-reperfusion injury model.
Male Brown-Norway rats underwent dissection of the right kidney. The animals were divided into 3 groups. The controls had the left renal blood vessels clamped for 90 minutes to induce ischemia, followed by reperfusion for 16 hours. In the intraperitoneal administration group, MnSOD was administered 30 minutes before ischemia and immediately before reperfusion. In the sham group, neither ischemia nor reperfusion was performed. After reperfusion, blood was collected, the left kidney was dissected and renal function and tissue injury were evaluated.
Serum creatinine and K(+), blood urea nitrogen, and aspartate aminotransferase activity decreased significantly, whereas serum Na(+) and renal function improved in the MnSOD group compared with the control and sham groups. On hematoxylin and eosin staining, the histological score indicated that acute tubular necrosis was significantly reduced by MnSOD administration. Periodic acid-Schiff staining was absent in the nonadministration group, whereas it persisted in the MnSOD group. In the proximal renal tubules a large proportion of anti-nitrotyrosine staining was present before but absent after MnSOD administration.
MnSOD administration improved renal function and reduced tissue injury. It may also reduce tissue injury in acute kidney transplant rejection and other tissue injuries caused by similar molecular mechanisms.
在急性肾移植排斥大鼠模型中，我们证明锰超氧化物歧化酶（MnSOD）活性显著降低，且MnSOD被过氧亚硝酸根（ONOO⁻）硝化，导致组织损伤。我们在大鼠肾缺血再灌注损伤模型中研究了外源性补充重组人MnSOD后组织损伤是否减轻。
雄性布朗-挪威大鼠行右肾切除术。动物被分为3组。对照组钳夹左肾血管90分钟以诱导缺血，随后再灌注16小时。在腹腔给药组，在缺血前30分钟和再灌注前即刻给予MnSOD。在假手术组，既不进行缺血也不进行再灌注。再灌注后，采集血液，解剖左肾并评估肾功能和组织损伤。
与对照组和假手术组相比，MnSOD组血清肌酐、钾离子、血尿素氮和天冬氨酸转氨酶活性显著降低，而血清钠离子和肾功能改善。苏木精-伊红染色显示，组织学评分表明给予MnSOD可显著减轻急性肾小管坏死。未给药组无过碘酸-希夫染色，而MnSOD组仍存在。在近端肾小管中，给予MnSOD前大部分有抗硝基酪氨酸染色，给药后则无。
给予MnSOD可改善肾功能并减轻组织损伤。它也可能减轻急性肾移植排斥及其他由相似分子机制引起的组织损伤中的组织损伤。
