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