Evidence against oxidant injury as a critical mediator of postischemic acute renal failure.
Evidence against oxidant injury as a critical mediator of postischemic acute renal failure.
复制标题
反对氧化损伤作为缺血后急性肾衰竭关键介质的证据。
DOI：
10.1152/ajprenal.1988.255.3.f450
复制
发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Zager,RA
中科院分区：
文献类型：
--
作者：
Gamelin,LM;Zager,RA
本研究的目的是通过记录缺血-缺氧损伤后的脂质过氧化，并证明抗氧化剂具有保护作用，从而证实活性氧（ROS）是缺血后肾损伤的关键介质。采用未校正和组织染色质校正的方法测定1)全肾组织皮质(C)、外髓条（OMS）、内髓条（IM），以及体内肾动脉闭塞（RAO; x 45 min）后15 min获得的C和OMS线粒体的丙二醛（MDA）浓度（脂质过氧化指标）；2)离体灌注肾缺血45分钟后15分钟获得C、OMS和IM全组织；3)缺氧45 min再氧15 min后分离的近端小管细胞（PTC）悬液。尽管在这些系统中都有明显的缺氧引起的损伤，但除了体内IM区域（仅通过未校正的MDA测定）外，MDA浓度没有显著升高。后者的升高可能归因于髓质血管充血，导致MDA测定中血红蛋白诱导的伪迹。60分钟的体内RAO加回流也没有提高MDA。为了验证MDA测定，PTC中加入4.2 mM H2O2。MDA突然增加了4倍。用两种抗氧化剂（别嘌呤醇或超氧化物歧化酶）预处理30和45分钟的RAO大鼠，均不能提供功能或形态上的保护。我们得出结论，活性氧可能不是体内缺血后急性肾功能衰竭的关键一致介质。
The purpose of this study is to confirm previous evidence for reactive oxygen species (ROS) as critical mediators of postischemic renal injury by documenting lipid peroxidation after ischemic-hypoxic insults and by demonstrating that antioxidants confer protection. Renal malondialdehyde (MDA) concentrations, an index of lipid peroxidation, were measured using uncorrected and tissue-chromagen-corrected methods in 1) cortical (C), outer medullary stripe (OMS), inner medullary (IM) whole renal tissues, and C and OMS mitochondria obtained 15 min after in vivo renal artery occlusion (RAO; x 45 min); 2) C, OMS, and IM whole tissues obtained 15 min after completing 45 min of ischemia in an isolated perfused kidney; and 3) isolated proximal tubular cell (PTC) suspensions after 45 min of hypoxia with 15 min of reoxygenation. Despite significant oxygen deprivation-induced injury in each of these systems, no significant rise in MDA concentrations could be documented, with the sole exception of the in vivo IM region (by uncorrected MDA assay only). The latter rise could be attributed to medullary vascular congestion causing a hemoglobin-induced artifact in the MDA assay. Sixty-minute in vivo RAO plus reflow also did not raise MDA. To validate the MDA assay 4.2 mM H2O2 was added to PTC. An abrupt fourfold rise in MDA resulted. Pretreatment of 30- and 45-min RAO rats with two antioxidants (allopurinol or superoxide dismutase) failed to confer functional or morphological protection. We conclude that ROS may not be critical consistent mediators of in vivo postischemic acute renal failure.