Heme oxygenase-1 protects against radiocontrast-induced acute kidney injury by regulating anti-apoptotic proteins
Heme oxygenase-1 protects against radiocontrast-induced acute kidney injury by regulating anti-apoptotic proteins
复制标题
DOI：
10.1038/sj.ki.5002447
复制
发表时间：
2007-10-01
影响因子：
19.6
通讯作者：
Abraham, N. G.
中科院分区：
文献类型：
--
作者：
Goodman, A. I.;Olszanecki, R.;Abraham, N. G.
放射造影剂被认为导致急性肾脏损伤的部分原因是通过增加活性氧的产生和增加细胞凋亡。在这项研究中，我们确定了血红素加氧酶-1是否可以预防或减少放射造影剂诱导的急性肾损伤，如果是，发生这种损伤的机制是什么。将硫代氨基甲酸钠应用于单肾切除、缺盐的雄性Sabra大鼠，造成急性肾损伤。钴原卟啉可诱导血红素加氧酶-1的表达，而亚锡则可抑制血红素加氧酶-1的表达。抑制血红素加氧酶加剧了肾脏损伤，这是通过增加血浆肌酐和超氧化物产生来衡量的。与未治疗的急性肾损伤大鼠相比，血红素加氧酶-1的诱导可阻止血浆肌酐的增加以及皮质和髓质中超氧化物的增加。血红素加氧酶-1的这种保护作用与增加抗凋亡蛋白Bcl2和Bclxl，减少促凋亡的caspase-3和caspase-9以及增加失活的Bax的表达有关。我们的研究表明，血红素加氧酶-1水平的增加对放射造影剂暴露所致的急性肾脏损伤具有保护作用。
Radiocontrast agents are thought to induce acute kidney injury in part through increased production of reactive oxygen species and increased cellular apoptosis. In this study we determined whether heme oxygenase-1 could prevent or reduce radiocontrast-induced acute kidney injury and, if so, what were the mechanisms by which this can occur. Sodium iothalamate was administered to uninephrectomized, salt-depleted male Sabra rats to initiate acute kidney injury. Heme oxygenase-1 was induced with cobalt protoporphyrin or inhibited with stannous mesoporphyrin. Inhibition of heme oxygenase exacerbated kidney injury as measured by an increase in plasma creatinine and in superoxide production. Heme oxygenase-1 induction prevented the increase in plasma creatinine and in superoxide in both the cortex and medulla compared to untreated rats with acute kidney injury. This protective effect of heme oxygenase-1 was associated with increased anti-apoptotic proteins Bcl-2 and Bcl-xl and a decrease of pro-apoptotic caspase-3 and caspase-9 along with increased expression of inactive BAX. Our study suggests that increased levels of heme oxygenase-1 are protective against acute kidney injury due to radiocontrast exposure.