间充质基质细胞衍生的细胞外囊泡通过增强大鼠体内Nrf2/ARE激活的抗氧化作用来预防急性肾损伤。
Mesenchymal Stromal Cell-Derived Extracellular Vesicles Protect Against Acute Kidney Injury Through Anti-Oxidation by Enhancing Nrf2/ARE Activation in Rats.
作者信息
Zhang Guangyuan, Zou Xiangyu, Huang Yeqing, Wang Feng, Miao Shuai, Liu Guohua, Chen Ming, Zhu Yingjian
机构信息
Department of Urology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
出版信息
Kidney Blood Press Res. 2016;41(2):119-28. doi: 10.1159/000443413. Epub 2016 Feb 20.
BACKGROUND/AIMS: Anti-oxidation is an effective strategy for curing acute kidney injury (AKI). Herein, we suggest that extracellular vesicles (EVs) derived from mesenchymal stromal cells (MSCs) might play an anti-oxidative role by enhancing Nrf2/ARE activation in AKI.
METHODS
EVs isolated from the conditioned medium of human Wharton's Jelly mesenchymal stromal cells and human foreskin fibroblast were intravenously injected in rats immediately after 45 min of unilateral kidney ischemia. Animals were sacrificed 24 h after injury.
RESULTS
Results showed that renal tubular injury was alleviated and renal function was improved by MSC-EVs. Cell apoptosis and sNGAL levels, which reflect kidney cell injury, were reduced. Moreover, MSC-EVs decreased oxidative stress in injured kidney tissues and NRK-52E cells under hypoxia injury. Nrf2/antioxidant response element (ARE) enhancement and HO-1 up-regulation were further observed after MSC-EV treatment both in vivo and in vitro.
CONCLUSIONS
MSC-EVs may protect against AKI possibly through anti-oxidation by enhancing Nrf2/ARE activation.
背景/目的：抗氧化是治疗急性肾损伤（AKI）的有效策略。在此，我们认为间充质基质细胞（MSC）衍生的细胞外囊泡（EV）可能通过增强AKI中的Nrf2/ARE激活发挥抗氧化作用。
方法
从人脐带华通氏胶间充质基质细胞和人包皮成纤维细胞的条件培养基中分离出的EV，在大鼠单侧肾脏缺血45分钟后立即静脉注射。在损伤后24小时处死动物。
结果
结果显示，MSC-EV减轻了肾小管损伤并改善了肾功能。反映肾细胞损伤的细胞凋亡和sNGAL水平降低。此外，MSC-EV降低了缺氧损伤下受损肾组织和NRK-52E细胞中的氧化应激。在体内和体外进行MSC-EV治疗后，进一步观察到Nrf2/抗氧化反应元件（ARE）增强和HO-1上调。
结论
MSC-EV可能通过增强Nrf2/ARE激活来抗氧化，从而预防AKI。
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