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苦马豆素通过下调 miR-429 保护 H9c2 细胞免受脂多糖诱导的凋亡和炎症损伤。

Swainsonine protects H9c2 cells against lipopolysaccharide-induced apoptosis and inflammatory injury via down-regulating miR-429.

机构信息

Department of Pediatrics, Jining No.1 People's Hospital, Jining, China.

Department of Nursing, Jining No.1 People's Hospital, Jining, China.

出版信息

Cell Cycle. 2020 Jan;19(2):207-217. doi: 10.1080/15384101.2019.1706902. Epub 2019 Dec 26.

Abstract

Pediatric myocarditis (PM) is usually related to myocardial dysfunction. Generally, 30% of PM patients will die or undergo heart transplantation. Swainsonine (SW) is a natural alkaloid and an anti-cancer substance. Our goal was to determine the roles of SW in PM in current study. H9c2 cells were pre-treated by lipopolysaccharide (LPS). Viability and apoptosis were evaluated utilizing CCK-8 assay and flow cytometry. Inflammatory cytokines' mRNA expression and production were assessed by western blot and ELISA. Western blot was utilized to distinguish apoptosis and immune-related factors expression. Sequentially, the abovementioned parameters were reassessed when miR-429 was overexpressed. LPS declined viability as well as raised apoptosis and inflammatory injury in H9c2 cells. SW alleviated apoptosis and inflammatory injury induced by LPS. MiR-429 expression was elevated by LPS and suppressed by SW. SW-induced the increasing of viability and the reduction of inflammatory injury were reversed by overexpression of miR-429. Eventually, SW inhibited p38MAPK/NF-κB pathway which activated by LPS via overexpressing miR-429. SW exerted its anti-apoptosis and anti-inflammatory function in LPS-treated H9c2 cells through p38MAPK/NF-κB pathway and down-regulation of miR-429.

摘要

儿科心肌炎(PM)通常与心肌功能障碍有关。一般来说,30%的 PM 患者会死亡或接受心脏移植。苦马豆素(SW)是一种天然生物碱和抗癌物质。在本研究中,我们的目的是确定 SW 在 PM 中的作用。用脂多糖(LPS)预处理 H9c2 细胞。利用 CCK-8 法和流式细胞术评估细胞活力和细胞凋亡。通过 Western blot 和 ELISA 评估炎症细胞因子的 mRNA 表达和产生。Western blot 用于区分细胞凋亡和免疫相关因子的表达。然后,当 miR-429 过表达时,重新评估上述参数。LPS 降低了 H9c2 细胞的活力,增加了细胞凋亡和炎症损伤。SW 减轻了 LPS 诱导的细胞凋亡和炎症损伤。LPS 上调了 miR-429 的表达,SW 抑制了 miR-429 的表达。LPS 激活的 p38MAPK/NF-κB 通路被 miR-429 过表达逆转,SW 诱导的活力增加和炎症损伤减少。最终,SW 通过过表达 miR-429 抑制了 p38MAPK/NF-κB 通路,从而发挥其在 LPS 处理的 H9c2 细胞中的抗凋亡和抗炎作用。

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