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薯蓣皂苷载锌纳米粒通过 microRNA-let 7i 信号通路缓解脂多糖诱导的急性肾损伤。

Dioscin-loaded zein nanoparticles alleviate lipopolysaccharide-induced acute kidney injury via the microRNA-let 7i signalling pathways.

机构信息

Department of Renal Medicine, Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian, China.

出版信息

IET Nanobiotechnol. 2021 Jul;15(5):465-472. doi: 10.1049/nbt2.12051. Epub 2021 May 12.

DOI:10.1049/nbt2.12051
PMID:34694758
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8675823/
Abstract

The present study investigates the potential role of dioscin (DIO) in the lipopolysaccharide (LPS)-induced kidney injury. For this purpose, DIO-loaded zein nanoparticles (DIO-ZNPs) were formulated and evaluated for physicochemical parameters. The DIO-ZNPs exhibited a controlled release of drug compared with that of the free drug suspension. Results showed that the cell viability of NRK-52E consistently decreased with the increase in LPS from 0.01 µg/ml to 2 µg/ml. When compared with LPS, DIO-induced NPs showed 1.10-, 1.32-, 1.57- and 1.92-fold increase in the cell viability for concentrations of 20 µg/ml, 50 µg/ml, 100 µg/ml and 200 µg/ml, respectively. DIO-ZNPs exhibited the most remarkable recovery in the cell proliferation compared with free DIO as shown by the cellular morphology analysis. Furthermore, Annexin-V staining analysis showed that the LPS-treated cells possess the lowest green fluorescence indicating fewer viable cells, whereas DIO-ZNPs exhibited the maximum green fluorescence comparable with that of the non-treated cells indicating maximum cell viability. Furthermore, the results show that DIO-ZNPs significantly increased the expression of miR-let-7i in the epithelial kidney cells, whereas the expression levels of TLR4 were significantly downregulated compared with that of the LPS-treated cells. In conclusion, miR-let-7i could be an interesting therapeutic target and nanoparticle-based DIO could be a potential candidate in the management of acute kidney injury.

摘要

本研究探讨了薯蓣皂素(DIO)在脂多糖(LPS)诱导的肾损伤中的潜在作用。为此,制备并评价了负载薯蓣皂素的玉米醇溶蛋白纳米粒(DIO-ZNPs)的理化参数。与游离药物混悬液相比,DIO-ZNPs 表现出药物的控制释放。结果表明,NRK-52E 细胞的细胞活力随着 LPS 浓度从 0.01μg/ml 增加到 2μg/ml 而持续下降。与 LPS 相比,浓度为 20μg/ml、50μg/ml、100μg/ml 和 200μg/ml 的 DIO 诱导的 NPs 分别使细胞活力增加了 1.10、1.32、1.57 和 1.92 倍。细胞形态分析显示,与游离 DIO 相比,DIO-ZNPs 表现出最显著的细胞增殖恢复。此外,Annexin-V 染色分析表明,LPS 处理的细胞具有最低的绿色荧光,表明活细胞较少,而 DIO-ZNPs 表现出与未处理细胞相当的最大绿色荧光,表明最大的细胞活力。此外,结果表明,DIO-ZNPs 显著增加了上皮肾细胞中 miR-let-7i 的表达,而 TLR4 的表达水平与 LPS 处理的细胞相比显著下调。总之,miR-let-7i 可能是一个有趣的治疗靶点,基于纳米粒的 DIO 可能是急性肾损伤管理的潜在候选药物。

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