Vitamin C alleviates LPS-induced myocardial injury by inhibiting pyroptosis via the ROS-AKT/mTOR signalling pathway

BMC Cardiovascular Disorders

Research

Yan Yan¹  Shimin Dong¹  Zhenzhen Sang¹  Xiaohua Bian¹  Yunxia Wei¹  Pu Zhang²  Meirong Zang³ 

[1] Department of Emergency, The Third Hospital of Hebei Medical University, Zi-Qiang Road No. 139, 050051, Shijiazhuang, Hebei, China;Department of Emergency, The Third Hospital of Hebei Medical University, Zi-Qiang Road No. 139, 050051, Shijiazhuang, Hebei, China;Department of Otolaryngology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China;Department of Haematology, The Third Hospital of Hebei Medical University, Shijiazhuang, Hebei, China;

关键词: Sepsis;    Myocardial injury;    Vitamin C;    Pyroptosis;    Reactive oxygen species (ROS);   

DOI  :  10.1186/s12872-022-03014-9

 received in 2022-05-11, accepted in 2022-12-15,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundThe efficacy of vitamin C in sepsis remains controversial. Whether vitamin C can alleviate lipopolysaccharide (LPS)-induced myocardial injury by inhibiting pyroptosis has not been studied. This study aimed to evaluate the effects of vitamin C on LPS-induced myocardial injury in vitro.MethodsH9C2 cells were treated with indicated concentrations of LPS, and the cell viability was then assessed by CCK-8 assay. The levels of lactate dehydrogenase (LDH), CK-MB, IL-18 and IL-1β were examined by enzyme-linked immunosorbent assay (ELISA). The levels of intracellular reactive oxygen species (ROS) were measured using the fluorescent probe dichlorodihydrofluorescein diacetate (DCFH-DA). Western blot assays were conducted to determine the levels of the ROS-associated protein nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) and pyroptosis-associated proteins, such as NOD-like receptor (NLR) family pyrin domain containing 3 (NLRP3), caspase-1 and gasdermin D (GSDMD). The AKT inhibitor MK-2206 was then applied to explore the signalling pathway. Finally, H9C2 cells were divided into the control group, LPS group, vitamin C + LPS group, and N-acetyl-l-cysteine (NAC) + LPS group. The intracellular ROS, levels of associated proteins, cell viability, and release of LDH, CK-MB, IL-18 and IL-1β were examined.ResultsLPS decreased cell viability and induced ROS and pyroptosis in H9C2 cells in a dose-dependent manner. Moreover, LPS activated the AKT/mTOR pathway in H9C2 cells. The AKT inhibitor MK-2206 protected H9C2 cells from LPS-induced death by suppressing pyroptosis, without changing intracellular ROS level. Vitamin C significantly inhibited intracellular ROS and cell pyroptosis in LPS-treated H9C2 cells. Moreover, vitamin C suppressed the activation of the AKT/mTOR pathway.ConclusionsOur data suggest that vitamin C alleviates LPS-induced myocardial injury by inhibiting pyroptosis via the ROS-AKT/mTOR signalling pathway and thus provide novel insights into the prevention of sepsis-induced myocardial dysfunction.

【 授权许可】

CC BY   
© The Author(s) 2022

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