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Hesperetin ameliorates lipopolysaccharide-induced acute lung injury via the miR-410/SOX18 axis.
Journal of Biochemical and Molecular Toxicology ( IF 3.2 ) Pub Date : 2020-08-06 , DOI: 10.1002/jbt.22588
Junying Dong 1 , Haiyan Zhou 1 , Hongqin Zhao 2 , Yanhong Zhao 2 , Can Chang 1
Affiliation  

Hesperetin (Hesp), a dihydroflavone, has a wide range of pharmacological activities, including antioxidant, anti‐inflammatory, and antitumor effects, as well as cardiovascular protection. It also has protective effects against acute lung injury (ALI); however, the exact mechanism remains unclear. In the present study, the protective effects and mechanism of Hesp in the lungs were investigated. Hematoxylin and eosin staining was used to examine pathological changes in the lungs. Enzyme‐linked immunosorbent assay was used to detect proinflammatory cytokine levels. In addition, reverse transcription‐quantitative polymerase chain reaction and Western blot analysis were used to observe the transcription and translation changes in the related genes, respectively. The results indicate that Hesp not only improves histopathological changes in the lungs but decreases the wet/dry ratio. In addition, total cell counts and the number of neutrophils and macrophages were lower in the bronchoalveolar fluid after Hesp treatment, consistent with the change in proinflammatory cytokine levels. MicroRNA‐410 (miR‐410) levels were significantly lower in the lung tissues of ALI mice and were reversed after Hesp treatment. Furthermore, miR‐410 overexpression due to injection with agomiR‐410 produced similar protective effects as Hesp. However, blocking miR‐410 inhibited the protective effects of Hesp in the lungs of ALI mice. In addition, miR‐410 has been shown to target the inhibition of sex determining region Y‐box 18 (SOX18), indicating that Hesp might alleviate inflammatory secretion by blocking the miR‐410/SOX18 axis. Thus, Hesp might be a potential agent for the treatment of ALI.

中文翻译:

橙皮素通过miR-410 / SOX18轴改善了脂多糖诱导的急性肺损伤。

橙皮素(Hesp)是一种二氢黄酮,具有广泛的药理活性,包括抗氧化,抗炎和抗肿瘤作用以及心血管保护作用。它还对急性肺损伤(ALI)具有保护作用;但是,确切的机制仍不清楚。在本研究中,研究了Hesp在肺中的保护作用和机制。苏木精和曙红染色用于检查肺部的病理变化。酶联免疫吸附法用于检测促炎细胞因子水平。此外,通过逆转录-定量聚合酶链反应和蛋白质印迹分析分别观察了相关基因的转录和翻译变化。结果表明,Hesp不仅改善了肺部的组织病理学变化,而且降低了干/湿比。此外,Hesp治疗后支气管肺泡液中的总细胞数以及中性粒细胞和巨噬细胞的数量均较低,这与促炎细胞因子水平的变化一致。MicroRNA-410(miR-410)的水平在ALI小鼠的肺组织中显着降低,在Hesp治疗后被逆转。此外,由于注射agomiR-410而导致的miR-410过表达产生了与Hesp类似的保护作用。但是,阻断miR-410会抑制Hesp对ALI小鼠肺部的保护作用。此外,已证明miR-410靶向抑制性别决定区Y-box 18(SOX18),这表明Hesp可能通过阻断miR-410 / SOX18轴来减轻炎症性分泌。
更新日期:2020-08-06
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