Cutrín J C, Zingaro B, Camandola S, Boveris A, Pompella A, Poli G
Department of Clinical and Biological Sciences, University of Turin, and A.Fa.R.-Fatebenefratelli Hospital, Turin, Italy. juan.cutrin@ sluigi.unito.it
Kidney Int. 2000 Feb;57(2):526-33. doi: 10.1046/j.1523-1755.2000.00871.x.
A variety of mechanisms have been considered in the pathogenesis of the cell damage occurring in the kidney that is undergoing transient ischemia. However, little information is available about the role of oxidative stress in building up the tissue injury in the hypoxic organ during short-term ischemia.
After a standard brief period (25 min) of unilateral kidney ischemia in rats, pretreated or not with acivicin (60 micromol/L/kg i.v.), tissue samples from both ischemic and not ischemic kidneys were obtained to measure malondialdehyde (MDA) and glutathione (GSH) content, gamma glutamyl transpeptidase (GGT) activity by spectrophotometry, localization and intensity of enzyme activity, and tissue damage by histochemistry.
GGT activity was found to be increased in both cortical and medullar zones of the ischemic kidneys, where the GSH level was only slightly decreased and the MDA level, in contrast, was markedly increased; in parallel, the cytosolic volume of the proximal tubular (PT) cells showed a significant increment. The animal pretreatment with acivicin, a specific inhibitor of GGT, besides preventing the up-regulation of the enzyme during ischemia, afforded good protection against the observed changes of MDA and GSH tissue levels, as well as of tubular cell volume.
Ex vivo data supporting a net pro-oxidant effect of up-regulated GGT during short-term ischemia of rat kidney have been obtained. The enzyme stimulation appears to contribute to the renal morphological damage exerted by a brief hypoxic condition at the level of PT cells. The actual impact on kidney function by GGT-dependent oxidative damage during transient ischemia and the potential protective action of GGT inhibitors require subsequent investigation.
在经历短暂缺血的肾脏中发生的细胞损伤的发病机制中，已经考虑了多种机制。然而，关于氧化应激在短期缺血期间低氧器官组织损伤形成中的作用，目前所知甚少。
在大鼠单侧肾脏缺血标准短暂时间（25分钟）后，无论是否用阿西维辛（60微摩尔/千克静脉注射）预处理，获取缺血和未缺血肾脏的组织样本，通过分光光度法测量丙二醛（MDA）和谷胱甘肽（GSH）含量、γ-谷氨酰转肽酶（GGT）活性、酶活性的定位和强度，并通过组织化学检测组织损伤。
发现在缺血肾脏的皮质和髓质区域GGT活性均增加，其中GSH水平仅略有下降，而MDA水平则明显升高；同时，近端小管（PT）细胞的胞质体积显著增加。用阿西维辛（一种GGT特异性抑制剂）对动物进行预处理，除了在缺血期间防止酶的上调外，还对观察到的MDA和GSH组织水平变化以及肾小管细胞体积变化提供了良好的保护作用。
已获得体外数据支持大鼠肾脏短期缺血期间上调的GGT具有净促氧化作用。酶的刺激似乎导致了短暂缺氧条件在PT细胞水平上对肾脏造成的形态学损伤。短暂缺血期间GGT依赖性氧化损伤对肾功能的实际影响以及GGT抑制剂的潜在保护作用需要后续研究。
