KDM2B overexpression prevents myocardial ischemia‑reperfusion injury in rats through regulating inflammatory response via the TLR4/NF‑κB p65 axis

Wei,Zijie; Luo,Lihua; Hu,Shuo; Tian,Rongcheng; Liu,Ziyou

doi:10.3892/etm.2021.11077

KDM2B overexpression prevents myocardial ischemia‑reperfusion injury in rats through regulating inflammatory response via the TLR4/NF‑κB p65 axis

Authors:
- Zijie Wei
- Lihua Luo
- Shuo Hu
- Rongcheng Tian
- Ziyou Liu
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Affiliations: Department of Cardiac Intensive Care, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China, Department of Nephrology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China, Department of Cardiac Surgery, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China, Department of Emergency, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China
Published online on: December 17, 2021 https://doi.org/10.3892/etm.2021.11077
Article Number: 154
Copyright: © Wei et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Histone modifier lysine‑specific demethylase 2B (KDM2B) has been previously reported to activate the inflammatory response by transcription initiation of the IL‑6 gene. However, the effects of KDM2B on the inflammatory response during myocardial ischemia‑reperfusion (I/R) injury and corresponding mechanisms remain poorly understood. The present study aimed to investigate the role and mechanism of KDM2B in myocardial I/R injury. Therefore, a myocardial I/R injury model was established in rats through coronary artery ligation. Adeno‑associated virus‑encoding KDM2B and small interfering RNA‑KDM2B were designed to determine the effects of KDM2B on myocardial I/R injury using H&E staining and a TUNEL assay in the myocardial tissues. Reverse transcription‑quantitative PCR and western blotting were performed to detect the mRNA and protein expression levels of KDM2B, toll‑like receptor 4 (TLR4), NF‑κB p65 and NOD‑, LRR‑ and pyrin domain‑containing protein 3 (NLRP3). ELISA was used to detect the levels of TNF‑α, IL‑6 and IL‑1β in the peripheral blood samples. Pathological analysis demonstrated that the cells in the model group were disordered, with a large area of necrosis and neutrophil infiltration. Knocking down KDM2B expression significantly upregulated the mRNA and protein expression levels of TLR4, NLRP3, NF‑κB p65 and the ratio of phosphorylated (p)‑p65 to p65. KDM2B knockdown also significantly increased the levels of IL‑1β, IL‑6 and TNF‑α in the peripheral blood, which aggravated myocardial injury and promoted the apoptosis of myocardial cells. However, overexpression of KDM2B downregulated the mRNA and protein expression levels of TLR4, NLRP3, NF‑κB P65, the ratio of p‑p65 to p65 whilst reducing the levels of IL‑1β, IL‑6 and TNF‑α in the peripheral blood, which markedly improved myocardial injury and significantly inhibited the apoptosis of cells in myocardial tissue. In conclusion, the results indicated that overexpression of KDM2B may prevent myocardial I/R injury in rats by reducing the inflammatory response through regulation of the TLR4/NF‑κB p65 axis.

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