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枸杞多糖通过下调 miR-122 保护 H9c2 细胞免受低氧损伤。

Lycium barbarum polysaccharides protects H9c2 cells from hypoxia-induced injury by down-regulation of miR-122.

机构信息

Department of Painless Endoscopy, Jining No.1 People's Hospital, Jining 272011, Shandong, China.

Department of Cardiology, Jining No.1 People's Hospital, Jining 272011, Shandong, China.

出版信息

Biomed Pharmacother. 2019 Feb;110:20-28. doi: 10.1016/j.biopha.2018.11.012. Epub 2018 Nov 17.

Abstract

BACKGROUND

Lycium barbarum polysaccharides (LBPs) are major ingredients of fructus lycii, which have multiple pharmacological activities, such as antioxidant, neuroprotective, and anti-inflammatory activities. This study attempted to reveal the potential of LBPs in hypoxia-injured H9c2 cells and the possible underlying mechanisms.

METHODS

H9c2 cells were treated by 300 μg/mL LBPs for 24 h upon hypoxia. Subsequently, the changes in cell viability, migration and apoptosis were evaluated. pre-miR-122 or miR-122 sponge was transfected into H9c2 cells to investigate whether miR-122 was involved in the mechanisms of LBPs' action. Besides, an animal model of myocardial infarction (MI) was established, and the in vivo effects of LBPs were further investigated.

RESULTS

LBPs increased cell viability, down-regulated p53, p21 and p16 protein expressions, improved migration, and repressed apoptosis in hypoxia-injured H9c2 cells. miR-122 was highly expressed in response to hypoxia, while was down-regulated by addition of LBPs. The protective actions of LBPs in hypoxia-injured H9c2 cells were attenuated by miR-122 overexpression, while were accelerated by miR-122 suppression. Also, LBPs-induced the activation of MEK/ERK and AMPK signaling pathways were attenuated by miR-122 overexpression, and were accelerated by miR-122 suppression. in vivo investigation revealed that, MI rats administrated with LBPs decreased infarct size and improved cardiac function via down-regulation of miR-122.

CONCLUSION

LBPs exhibited in vitro and in vivo cardioprotective activities via down-regulating miR-122. LBPs may have potential for the treatment of acute myocardial infarction (AMI).

摘要

背景

枸杞多糖(LBPs)是枸杞的主要成分,具有多种药理活性,如抗氧化、神经保护和抗炎活性。本研究试图揭示 LBPs 在缺氧损伤的 H9c2 细胞中的潜在作用及其可能的机制。

方法

H9c2 细胞在缺氧条件下用 300μg/mL LBPs 处理 24h。随后,评估细胞活力、迁移和凋亡的变化。将 pre-miR-122 或 miR-122 海绵转染到 H9c2 细胞中,以研究 miR-122 是否参与了 LBPs 作用的机制。此外,还建立了心肌梗死(MI)动物模型,进一步研究了 LBPs 的体内作用。

结果

LBPs 增加了缺氧损伤的 H9c2 细胞的活力,下调了 p53、p21 和 p16 蛋白的表达,改善了迁移,并抑制了凋亡。miR-122 在缺氧时高表达,而加入 LBPs 后则下调。LBPs 在缺氧损伤的 H9c2 细胞中的保护作用被 miR-122 过表达所减弱,而被 miR-122 抑制所加速。此外,LBPs 诱导的 MEK/ERK 和 AMPK 信号通路的激活被 miR-122 过表达所减弱,而被 miR-122 抑制所加速。体内研究表明,LBPs 通过下调 miR-122 减轻了 MI 大鼠的梗死面积并改善了心脏功能。

结论

LBPs 通过下调 miR-122 表现出体外和体内的心脏保护活性。LBPs 可能具有治疗急性心肌梗死(AMI)的潜力。

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