The orphan nuclear receptor RORα is a potential endogenous protector in renal ischemia/ reperfusion

《肾缺血再灌注损伤》

题目：《The orphan nuclear receptor RORα is a potential endogenous protector in renal ischemia/ reperfusion injury》（译：《孤核受体 RORα是肾缺血再灌注损伤的潜在内源性保护因子》）
Abstract：Emerging evidence indicates that retinoid-related orphan receptor (ROR)α, a member of the ROR nuclear receptor subfamily, mediates key cellular adaptions to hypoxia and contributes to the pathophysiology of many disease states. However, the effects of RORα in renal ischemia/reperfusion (I/R) injury remain unclear. Wild-type (WT) C57 black 6 (C57BL/6) mice and RORα-deficient stagger [ROR(sg/sg)] mice and their WT litter-mates were used for in vivo studies. The renal I/R injury model was induced by bilateral renal pedicle clamping for 35 min. Human proximal tubule cell line cells were treated with hypoxia (1% oxygen) to establish the cell hypoxia/reoxygenation (H/R) model. We investigated the renal expression and biologic function of RORα, and we found that RORα was significantly down-regulated after renal I/R injury. ROR(sg/sg) mice displayed dramatically augmented renal dysfunction and morphologic damage compared with WT mice at 24 h post-I/R. Further study revealed that the detrimental effects of RORα deficiency were attributable to tubular epithelial cell apoptosis and, consequently, renal inflammation and oxidative stress. The proapoptotic effect of RORα deficiency was associated with aggravated mitochondrial dysfunction in renal tubular cells after I/R. However, pretreatment of C57BL/6 mice with the RORα agonist SR1078 ameliorated I/R-induced renal dysfunction and damage and elicited a concomitant decrease in tubular epithelial cell apoptosis. In summary, our study provides experimental evidence showing that RORα is a novel endogenous protector against renal I/R injury and that ROR-α activation is a promising therapeutic strategy for the prevention of acute kidney injury.（译：最新证据表明，视网膜相关孤儿受体（ROR）α，ROR核受体亚家族的成员，调解关键的细胞适应缺氧，并有助于许多疾病状态的病理生理学。然而，RORα对肾缺血/输液（I/R）损伤的影响尚不清楚。野生型（WT） C57 黑色 6 （C57BL/6）小鼠和 ROR+ 缺陷交错 [ROR （sg/sg）] 小鼠及其 WT 垃圾伴侣用于体内研究。肾I/R损伤模型是由双边肾足骨夹紧35分钟引起的。人类近邻管状细胞线细胞接受缺氧（1%氧）治疗，以建立细胞缺氧/再氧化（H/R）模型。我们调查了 RORα 的肾脏表达和生物功能，发现 RORα 在肾 I/R 损伤后受到显著降低调节。与WT小鼠相比，ROR（sg/sg）小鼠在I/R后24小时内表现出显著增加的肾功能障碍和形态损伤。进一步研究表明，RORα缺乏症的有害影响归因于管状上皮细胞凋亡，因此，肾炎和氧化应激。ROR®缺乏症的原流行效应与I/R后肾管状细胞中严重的线粒体功能障碍有关。然而，C57BL/6小鼠与RORα激动剂SR1078的预处理改善了I/R引起的肾功能障碍和损伤，并导致管状上皮细胞凋亡的随之减少。总之，我们的研究提供了实验证据，表明RORα是一种新型的内源性保护剂，可以预防肾I/R损伤，而ROR-α激活是预防急性肾损伤的有希望的治疗策略。孤儿核受体RORα是肾缺血/输液损伤中潜在的内源性保护剂。）
期刊：Faseb Journal
Impact Factor: 5.595
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研究作者：蔡洁茹
研究单位：上海中山医院肾内科
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