Biogenic Nanoselenium Particles Effectively Attenuate Oxidative Stress-Induced Intestinal Epithelial Barrier Injury by Activating the Nrf2 Antioxidant Pathway
Biogenic Nanoselenium Particles Effectively Attenuate Oxidative Stress-Induced Intestinal Epithelial Barrier Injury by Activating the Nrf2 Antioxidant Pathway
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DOI：
10.1021/acsami.7b03377
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发表时间：
2017-05-03
影响因子：
9.5
通讯作者：
Wang, Yizhen
中科院分区：
文献类型：
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作者：
Song, Deguang;Cheng, Yuanzhi;Wang, Yizhen
在本研究中，一种新的形式的硒纳米粒子（生物纳米硒（BNS）粒子）的合成使用细菌。研究了BNS颗粒对氧化应激诱导的肠屏障功能障碍的保护作用及其内在机制，并与硒代蛋氨酸（SeMet）和化学合成的纳米硒（Nano-Se）颗粒进行了比较。BNS颗粒的表征表明，它们是单分散和均匀的球体，平均尺寸为139.43 +/- 7.44 nm。在小鼠肠道氧化应激模型中，发现BNS颗粒比SeMet和Nano-Se更有效地保护小鼠肠道屏障功能和维持肠道氧化还原稳态。猪空肠上皮（IPEC-J2）细胞的体外实验证实了BNS颗粒对氧化应激的更强的上皮屏障保护作用，减少细胞凋亡和改善细胞氧化还原状态。BNS激活核因子（红细胞衍生的-2）样2（Nrf 2）并以剂量和时间依赖性方式增加其下游基因的表达，包括硫氧还蛋白还原酶（TXNRD）-1、NADPH脱氢酶（NQO）-1、血红素加氧酶（HO）-1和硫氧还蛋白（Trx）。相比之下，硒蛋氨酸和纳米硒仅增强硒酶TXNRD-1和谷胱甘肽过氧化物酶（GPx）-1的活性，表明硒供体的作用。此外，敲低Nrf 2显著阻断BNS的抗氧化作用，证实BNS通过激活Nrf 2及其下游基因保护肠屏障免受氧化应激诱导的损伤。我们的研究结果表明，BNS是一个有前途的硒物种，在治疗氧化应激相关的肠道疾病的潜在应用。
In the present study, a new form of selenium nanoparticle (biogenic nanoselenium (BNS) particles) was synthesized using bacteria. The protection of BNS particles against oxidative stress-induced intestinal barrier dysfunction and the inherent mechanisms of this process were investigated, and selenomethionine (SeMet) and chemically synthesized nanoselenium (Nano-Se) particles were used for comparison. Characterization of BNS particles revealed that they were monodispersed and homogeneous spheres, with an average size of 139.43 +/- 7.44 nm. In the mouse model of intestinal oxidative stress, BNS particles were found to protect the mouse intestinal barrier function and preserve intestinal redox homeostasis more efficiently than SeMet and Nano-Se. In vitro experiments with porcine jejunum epithelial (IPEC-J2) cells verified the stronger epithelial barrier-protecting effect of BNS particles against oxidative stress, with reduced cell apoptosis and an improved cell redox state. BNS activated the nuclear factor (erythroid-derived-2)-like 2 (Nrf2) and increased the expression of its downstream genes, including thioredoxin reductase (TXNRD)-1, NADPH dehydrogenase (NQO)-1, heme oxygenase (HO)-1, and thioredoxin (Trx), in dose- and time-dependent manners. In contrast, SeMet and Nano-Se merely enhanced the activity of the selenoenzymes TXNRD-1 and glutathione peroxidase (GPx)-1, indicating the role of selenium donors. Moreover, the knock down of Nrf2 significantly blocked the antioxidative effect of BNS, confirming that BNS protects the intestinal barrier from oxidative stress-induced damage by activating Nrf2 and its downstream genes. Our results suggest that BNS is a promising selenium species with potential application in treating oxidative stress-related intestinal diseases.