Retinoic acid attenuates contrast-induced acute kidney injury in a miniature pig model.
Retinoic acid attenuates contrast-induced acute kidney injury in a miniature pig model.
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DOI：
10.1016/j.bbrc.2019.03.013
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发表时间：
2019-04
影响因子：
3.1
通讯作者：
Junxia Wu;X. Wan;H. Zhang;Wenwen Li;Mengqing Ma;Bin-bin Pan;Xiubin Liang;Changchun Cao
中科院分区：
文献类型：
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作者：
Junxia Wu;X. Wan;H. Zhang;Wenwen Li;Mengqing Ma;Bin-bin Pan;Xiubin Liang;Changchun Cao
造影剂诱导的急性肾损伤（CI-AKI）已成为医院获得性AKI的第三大原因。维甲酸（Retinoic acid， RA）是维生素A的主要衍生物，在缺血-再灌注- aki和UUO模型中具有预防和治疗作用，但对CI-AKI的作用知之甚少。本研究旨在探讨RA对CI-AKI的影响及其机制。方法采用颈外静脉置管和单剂量碘己醇脱水建立新型猪CI-AKI微型模型。测定Bun、Scr、血清和尿RBP及β-MG水平。进行肾脏组织学、TEM检查、LDH检测、TUNEL检测、GFP-LC3质粒转染和western blotting检测。结果CI-AKI后Bun、Scr、血清和尿RBP、β-MG水平升高，RA预处理后降低。CI-AKI后肾脏组织学表现为泡沫变性、小管扩张，RA预处理后组织损伤明显减轻。RA减轻CI-AKI后肾纤维化。在体外，RA可保护近端tec免受碘己醇诱导的损伤。RA在体内外均抑制TECs凋亡，激活自噬。结论ra可减轻CI-AKI，减轻CI-AKI后肾纤维化。RA对CI-AKI的保护作用涉及自噬激活和细胞凋亡抑制。RA可能成为未来预防和治疗CI-AKI的新药物。
BackgroundContrast-induced acute kidney injury (CI-AKI) has been the third leading cause of hospital-acquired AKI. Retinoic acid (RA), the main derivative of vitamin A, has preventative and therapeutic effects in ischemia-reperfusion-AKI and UUO models, but little is known about its effects on CI-AKI. This study aimed to explore the effects of RA on CI-AKI as well as the underlying mechanisms.MethodsWe established a new miniature pig model of CI-AKI by catheterizing the external jugular vein and injecting a single dose of iohexol after dehydration. Bun, Scr, serum and urinary RBP and β-MG levels were measured. Renal histological, TEM examination, LDH assays, TUNEL assays, GFP-LC3 plasmid transfection and western blotting were performed.ResultsThe levels of Bun, Scr, serum and urinary RBP and β-MG were increased after CI-AKI and decreased by RA pretreatment. The renal histology showed foamy degeneration and dilated tubules after CI-AKI, and the tissue damage was alleviated significantly by RA pretreatment. RA mitigated renal fibrosis after CI-AKI. In vitro, RA protected proximal TECs against iohexol-induced injury. RA inhibited TECs apoptosis and activated autophagy in vivo and in vitro.ConclusionsRA alleviates CI-AKI and mitigates renal fibrosis after CI-AKI. Autophagy activation and apoptosis inhibition are involved in the protective effect of RA on CI-AKI. RA may be a new agent for the prevention and therapeutic treatment of CI-AKI in the future.