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多孔 Se@SiO 纳米球通过抗氧化应激减轻缺血再灌注(I/R)引起的急性肾损伤(AKI)和炎症。

Porous Se@SiO nanospheres attenuate ischemia/reperfusion (I/R)-induced acute kidney injury (AKI) and inflammation by antioxidative stress.

机构信息

Department of Nephrology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China,

Trauma Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Int J Nanomedicine. 2018 Dec 27;14:215-229. doi: 10.2147/IJN.S184804. eCollection 2019.

Abstract

OBJECTIVES

Acute kidney injury (AKI) is a growing global health concern, and is associated with high rates of mortality and morbidity in intensive care units. Se is a trace element with antioxidant properties. This study aimed to determine whether porous Se@SiO nanospheres could relieve oxidative stress and inflammation in ischemia/reperfusion (I/R)-induced AKI.

METHODS

Male 6- to 8-week-old C57bl/6 mice were divided into four groups: sham + saline, sham + Se@SiO, I/R + saline, and I/R + Se@SiO. Mice in the I/R groups experienced 30 minutes of bilateral renal I/R to induce an AKI. Porous Se@SiO nanospheres (1 mg/kg) were intraperitoneally injected into mice in the I/R + Se@SiO group 2 hours before I/R, and the same dose was injected every 12 hours thereafter. Hypoxia/reoxygenation (H/R) was used to mimic I/R in vitro. PBS was used as a control treatment. Human kidney 2 cells were seeded into 12-well plates (5×10 cells/well) and divided into four groups: control + PBS group, control + Se@SiO group, H/R + PBS group, and H/R + Se@SiO group (n=3 wells). We then determined the expression levels of ROS, glutathione, inflammatory cytokines and proteins, fibrosis proteins, and carried out histological analysis upon kidney tissues.

RESULTS

In vitro, intervention with porous Se@SiO nanospheres significantly reduced levels of ROS (<0.05), inflammatory cytokines (<0.05), and inflammation-associated proteins (<0.05). In vivo, tubular damage, cell apoptosis, and interstitial inflammation during AKI were reduced significantly following treatment with porous Se@SiO nanospheres. Moreover, the occurrence of fibrosis and tubular atrophy after AKI was attenuated by porous Se@SiO nanospheres.

CONCLUSION

Porous Se@SiO nanospheres exhibited a protective effect in I/R-induced AKI by resisting oxidative stress and inflammation. This suggests that porous Se@SiO nanospheres may represent a new therapeutic method for AKI.

摘要

目的

急性肾损伤(AKI)是一个日益严重的全球健康问题,与重症监护病房的高死亡率和发病率有关。硒是一种具有抗氧化特性的微量元素。本研究旨在确定多孔 Se@SiO 纳米球是否可以缓解缺血/再灌注(I/R)诱导的 AKI 中的氧化应激和炎症。

方法

雄性 6-8 周龄 C57bl/6 小鼠分为四组:假手术+生理盐水、假手术+Se@SiO、I/R+生理盐水和 I/R+Se@SiO。I/R 组小鼠经历 30 分钟双侧肾 I/R 以诱导 AKI。多孔 Se@SiO 纳米球(1mg/kg)在 I/R 前 2 小时腹腔注射到 I/R+Se@SiO 组小鼠中,此后每 12 小时注射一次相同剂量。缺氧/复氧(H/R)用于体外模拟 I/R。PBS 用作对照处理。人肾 2 细胞接种到 12 孔板(5×10 个细胞/孔)中,分为四组:对照+PBS 组、对照+Se@SiO 组、H/R+PBS 组和 H/R+Se@SiO 组(n=3 孔)。然后,我们测定 ROS、谷胱甘肽、炎症细胞因子和蛋白、纤维化蛋白的表达水平,并对肾组织进行组织学分析。

结果

在体外,多孔 Se@SiO 纳米球的干预显著降低了 ROS(<0.05)、炎症细胞因子(<0.05)和炎症相关蛋白(<0.05)的水平。在体内,用多孔 Se@SiO 纳米球治疗后,AKI 时肾小管损伤、细胞凋亡和间质炎症明显减少。此外,多孔 Se@SiO 纳米球减轻了 AKI 后纤维化和肾小管萎缩的发生。

结论

多孔 Se@SiO 纳米球通过抵抗氧化应激和炎症对 I/R 诱导的 AKI 表现出保护作用。这表明多孔 Se@SiO 纳米球可能代表 AKI 的一种新的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c155/6312062/d01a298c1f55/ijn-14-215Fig2.jpg

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