Trehalose attenuates renal ischemia-reperfusion injury by enhancing autophagy and inhibiting oxidative stress and inflammation
Trehalose attenuates renal ischemia-reperfusion injury by enhancing autophagy and inhibiting oxidative stress and inflammation
复制标题
海藻糖通过增强自噬、抑制氧化应激和炎症来减轻肾缺血再灌注损伤
DOI：
10.1152/ajprenal.00568.2019
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发表时间：
2020-04-01
影响因子：
4.2
通讯作者：
Huang, Songming
中科院分区：
文献类型：
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作者：
Liu, Suwen;Yang, Yunwen;Huang, Songming
肾缺血再灌注损伤（IR）是最常见的急性肾损伤之一，但临床上仍缺乏有效的治疗方法。海藻糖（Tres）是一种天然二糖，已被证明可以防止氧化应激，炎症和细胞凋亡。然而，它是否可以保护IR诱导的肾损伤需要研究。在体内实验中，C57131，161小鼠在肾IR手术前3天通过每日单次腹膜内注射用或不用Tre（g/kg）预处理。分析肾功能、细胞凋亡、氧化应激和炎症以评估肾损伤。在体外实验中，在缺氧/复氧条件下用或不用Tre处理小鼠近端肾小管细胞。Western blot分析、自噬通量检测和细胞凋亡实验检测Tre的自噬水平和抗凋亡作用。体内实验结果表明，Tre治疗可改善IR引起的肾损伤，改善肾组织学和肾功能，阻断肾损伤分子-1和中性粒细胞明胶酶相关脂质运载蛋白的表达。此外，自噬被Ire预处理沿着激活，同时抑制IR损伤诱导的细胞凋亡、氧化应激和炎症。体外实验结果表明，Tre处理激活了自噬，并对缺氧/复氧诱导的肾小管细胞凋亡和氧化应激具有保护作用。我们的研究结果表明，Tre保护对IR诱导的肾损伤，可能通过增强自噬和阻断氧化应激，炎症和凋亡，这表明其潜在的临床治疗肾IR损伤的用途。
Renal ischemia-reperfusion (IR) injury is one of the most common acute kidney injuries, but there is still a lack of effective treatment in the clinical setting. Trehalose (Tre), a natural disaccharide, has been demonstrated to protect against oxidative stress, inflammation, and apoptosis. However, whether it could protect against IR-induced renal injury needs to be investigated. In an in vivo experiment, C57131,161 mice were pretreated with or without Tre g/kg) through a daily single intraperitoneal injection from 3 days before renal IR surgery. Renal function, apoptosis, oxidative stress, and inflammation were analyzed to evaluate kidney injury. In an in vitro experiment, mouse proximal tubular cells were treated with or without Tre under a hypoxia/reoxygenation condition. Western blot analysis, autophagy flux detection, and apoptosis assay were performed to evaluate the level of autophagy and antiapoptotic effect of Tre. The in vivo results showed that the renal damage induced by IR was ameliorated by Tre treatment, as renal histology and renal function were improved and the enhanced protein levels of kidney injury molecule -1 and neutrophil gelatinase-associated lipocalin were blocked. Moreover, autophagy was activated by 'Ire pretreatment along with inhibition of the IR injury -induced apoptosis, oxidative stress, and inflammation. The in vitro results showed that Tre treatment activated autophagy and protected against hypoxia/reoxygenation-induced tubular cell apoptosis and oxidative stress. Our results demonstrated that Tre protects against IR-induced renal injury, possibly by enhancing autophagy and blocking oxidative stress, inflammation, and apoptosis, suggesting its potential use for the clinical treatment of renal IR injury.