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栀子苷通过上调 miR-145-5p 保护 PC12 细胞免受脂多糖诱导的炎症损伤。

Geniposide protects PC12 cells from lipopolysaccharide-evoked inflammatory injury via up-regulation of miR-145-5p.

机构信息

a Department of Orthopedics, China-Japan Union Hospital of Jilin University , Changchun , China.

b Department of Ophthalmology, The Second Hospital of Jilin University , Changchun , China.

出版信息

Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):2875-2881. doi: 10.1080/21691401.2019.1626406.

Abstract

Geniposide is an active ingredient with anti-apoptotic and anti-inflammatory properties. This study was to examine the effects of geniposide on a cell model of spinal cord injury (SCI). PC12 cells were administrated with geniposide before subjected to LPS. The effects of geniposide were analyzed by utilizing CCK-8 assay, apoptosis assay, ELISA, RT-qPCR and Western blot. We found that PC12 cells viability was unchanged by treating with geniposide. However, geniposide with concentrations of 200 or 300 μg/mL significantly mitigated LPS-evoked viability loss. Meanwhile, apoptosis driven by LPS was mitigated by geniposide, which accompanied with p53, Bax and cleaved caspase-3 down-regulation, and Bcl-2 up-regulation. Besides this, the expression and release of IL-1β, IL-6, IL-8 and TNF-α evoked by LPS were mitigated by geniposide. miR-145-5p was a target of geniposide. miR-145-5p expression was up-regulated by geniposide, and geniposide did not protect PC12 cells against LPS injury when miR-145-5p was silenced. Moreover, geniposide inhibited NF-κB and JNK pathways via up-regulating miR-145-5p. In short, the present work described the neuroprotective effects of geniposide by targeting miR-145-5p. Further mechanisms involved in geniposide's beneficial effects are correlated with the inhibited NF-κB and JNK pathways. Highlights Geniposide prevents LPS-induced injury in PC12 cells; Geniposide up-regulates miR-145-5p; Geniposide protects PC12 cells via up-regulation of miR-145-5p; Geniposide inhibits NF-κB and JNK pathways via up-regulation of miR-145-5p.

摘要

京尼平苷是一种具有抗凋亡和抗炎作用的活性成分。本研究旨在探讨京尼平苷对脊髓损伤(SCI)细胞模型的作用。PC12 细胞先用 LPS 处理,再用京尼平苷处理。通过 CCK-8 检测、凋亡检测、ELISA、RT-qPCR 和 Western blot 分析京尼平苷的作用。结果发现,用京尼平苷处理不会改变 PC12 细胞的活力,但浓度为 200 或 300μg/mL 的京尼平苷可显著减轻 LPS 引起的活力丧失。同时,京尼平苷减轻了 LPS 诱导的细胞凋亡,伴随 p53、Bax 和 cleaved caspase-3 下调,Bcl-2 上调。此外,京尼平苷还减轻了 LPS 诱导的 IL-1β、IL-6、IL-8 和 TNF-α的表达和释放。miR-145-5p 是京尼平苷的靶标。京尼平苷上调 miR-145-5p 的表达,当 miR-145-5p 被沉默时,京尼平苷不能保护 PC12 细胞免受 LPS 损伤。此外,京尼平苷通过上调 miR-145-5p 抑制 NF-κB 和 JNK 通路。总之,本研究描述了京尼平苷通过靶向 miR-145-5p 发挥神经保护作用。京尼平苷有益作用的进一步机制与抑制 NF-κB 和 JNK 通路有关。

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