关键词: Aerobic glycolysis ischemia–reperfusion injury miR-34c-5p/ALDOA axis myocardial scutellarin

来  源:   DOI:10.4103/ijabmr.ijabmr_415_23   PDF(Pubmed)

Abstract:
UNASSIGNED: Aerobic glycolysis has recently demonstrated promising potential in mitigating the effects of ischemia-reperfusion (IR) injury. Scutellarin (Scu) possesses various cardioprotective properties that warrant investigation. To mimic IR injury in vitro, this study employed hypoxia/reoxygenation (H/R) injury.
UNASSIGNED: First, we conducted an assessment of the protective properties of Scu against HR in H9c2 cells, encompassing inflammation damage, apoptosis injury, and oxidative stress. Then, we verified the effects of Scu on the Warburg effect in H9c2 cells during HR injury. The findings indicated that Scu augmented aerobic glycolysis by upregulating p-PKM2/PKM2 levels. Following, we built a panel of six long noncoding RNAs and seventeen microRNAs that were reported to mediate the Warburg effect. Based on the results, miR-34c-5p was selected for further experiments. Then, we observed Scu could mitigate the HR-induced elevation of miR-34c-5p. Upregulation of miR-34c-5p could weaken the beneficial impacts of Scu in cellular viability, inflammatory damage, oxidative stress, and the facilitation of the Warburg effect. Subsequently, our investigation revealed a decrease in both ALDOA mRNA and protein levels following HR injury, which could be restored by Scu administration. Downregulation of ALDOA or Mimic of miR-34c-5p could reduce these effects induced by Scu.
UNASSIGNED: Scu provides cardioprotective effects against IR injury by upregulating the Warburg effect via miR-34c-5p/ALDOA.
摘要:
有氧糖酵解最近在减轻缺血再灌注(IR)损伤的影响方面表现出了有希望的潜力。Scutellarin(Scu)具有各种心脏保护特性,值得研究。为了在体外模拟IR损伤,本研究采用缺氧/复氧(H/R)损伤。
首先,我们对Scu对H9c2细胞中HR的保护特性进行了评估,包括炎症损伤,凋亡损伤,和氧化应激。然后,我们验证了Scu对HR损伤期间H9c2细胞Warburg效应的影响。研究结果表明,Scu通过上调p-PKM2/PKM2水平来增强有氧糖酵解。Follows,我们构建了一组6种长非编码RNA和17种microRNA,据报道它们可以介导Warburg效应.根据结果,选择miR-34c-5p用于进一步的实验。然后,我们观察到Scu可以减轻HR诱导的miR-34c-5p升高。上调miR-34c-5p可以削弱Scu对细胞活力的有益影响,炎性损伤,氧化应激,以及Warburg效应的促进作用。随后,我们的调查显示HR损伤后ALDOAmRNA和蛋白质水平均下降,可以由Scu管理部门恢复。ALDOA的下调或miR-34c-5p的模拟可以减少Scu诱导的这些作用。
Scu通过miR-34c-5p/ALDOA上调Warburg效应,对IR损伤提供心脏保护作用。
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