Role of heme oxygenase-1 in protection of the kidney after hemorrhagic shock
Role of heme oxygenase-1 in protection of the kidney after hemorrhagic shock
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DOI：
10.3892/ijmm_00000430
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发表时间：
2010-07-01
影响因子：
5.4
通讯作者：
Morita, Kiyoshi
中科院分区：
文献类型：
--
作者：
Arimori, Yutaka;Takahashi, Toru;Morita, Kiyoshi
失血性休克复苏（HSR）引起氧化应激，导致多器官损伤。肾脏是HSR介导的氧化性组织损伤的靶器官之一。血红素加氧酶（HO）-1是血红素催化剂中的限速酶，由氧化应激诱导;它保护组织免受氧化损伤。本研究的目的是研究HSR后肾脏HO-1诱导的作用。使大鼠经受失血性休克以达到30 mmHg的平均动脉压持续60分钟，随后用流出的血液复苏。HSR导致肾小管上皮细胞中功能性HO-1蛋白的显著增加，而HSR仅导致肿瘤坏死因子（TNE）-α和诱导型一氧化氮合酶（iNOS）基因表达的轻微增加，并且仅在HO-1表达不存在的肾细胞中激活的caspase-3蛋白表达。HSR也导致Bcl-2基因表达的显着增加。预处理的HSR动物与锡-中卟啉（0.5 μ mol/kg），HO活性的特异性竞争性抑制剂，导致HO活性的显着降低，并加剧组织炎症和凋亡细胞死亡的判断显着增加的TNF-α和iNOS的表达，并在激活的caspase-3阳性细胞，并显着减少Bcl-2的表达，分别。这些研究结果表明，HO-1诱导是一种适应性反应，对HSR诱导的氧化应激，是必不可少的保护肾小管上皮细胞从氧化损伤，通过其抗炎和抗凋亡特性。
Hemorrhagic shock followed by resuscitation (HSR) causes oxidative stress, which results in multiple organ damage. The kidney is one of the target organs of HSR-mediated oxidative tissue injury. Heme oxygenase (HO)-1, the rate-limiting enzyme in heme catabolism, is induced by oxidative stress; it protects against oxidative tissue injuries. The aim of the present study was to examine the role of renal HO-1 induction after HSR. Rats were subjected to hemorrhagic shock to achieve a mean arterial pressure of 30 mmHg for 60 min, followed by resuscitation with the shed blood. HSR resulted in a significant increase in functional HO-1 protein in the tubular epithelial cells of the kidney, whereas HSR resulted in only a slight increase in gene expression of tumor necrosis factor (TNE)-alpha and inducible nitric oxide synthase (iNOS), and in protein expression of activated caspase-3 solely in renal cells where HO-1 expression was absent. HSR also resulted in a significant increase in Bcl-2 gene expression. Pretreatment of HSR animals with tin-mesoporphyrin (0.5 mu mol/kg), a specific competitive inhibitor of HO activity, resulted in a significant decrease in HO activity and exacerbated tissue inflammation and apoptotic cell death as judged by the marked increase in expression of TNF-alpha and iNOS, and in activated caspase-3-positive cells, and the significant reduction in Bcl-2 expression, respectively. These findings indicate that HO-1 induction is an adaptive response to HSR-induced oxidative stress and is essential for protecting tubular epithelial cells from oxidative damage through its anti-inflammatory and anti-apoptotic properties.