Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, PR China; Cardiovascular Research Institute of Wuhan University, Wuhan 430060, Hubei Province, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, Hubei Province, PR China.
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei Province, PR China; Cardiovascular Research Institute of Wuhan University, Wuhan 430060, Hubei Province, PR China; Hubei Key Laboratory of Cardiology, Wuhan 430060, Hubei Province, PR China.
Eur J Pharmacol. 2019 Feb 5;844:79-86. doi: 10.1016/j.ejphar.2018.11.025. Epub 2018 Nov 17.
Myeloid differentiation protein 1(MD1), also known as lymphocyte antigen 86 (LY86), plays an important role in the toll-like receptor 4 (TLR4) signaling pathway. Recent studies show that MD1 is involved in regulating pressure overload-induced cardiac structural and electrical remodeling. However, the effect of MD1 on myocardial ischemia-reperfusion (I/R) injury and I/R related arrhythmia remains unknown. To further investigate that, the present study used MD1-knockout (MD1-KO) mice to study the role of MD1 in regulating myocardial I/R injury and its electrophysiology. The results demonstrate that the loss of MD1 led to a larger infarct size, increased activity of cardiac injury markers, aggravated histological damage, worsened cardiac function and decreased survival rate after myocardial I/R. Meanwhile, MD1 deficiency also aggravated inflammatory responses, promoted cardiomyocyte apoptosis and increased susceptibility to ventricular arrhythmia in mice subjected to myocardial I/R. Furthermore, loss of MD1 enhanced the activation of toll-like receptor 4 (TLR4) / nuclear factor kappa B (NF-κB) signaling pathway after myocardial I/R. Therefore, loss of MD1 exacerbated myocardial I/R injury and increased the susceptibility to ventricular arrhythmia, both of which are possibly related to the up-regulation of TLR4/NF-κB signaling pathway.
髓系分化蛋白 1（MD1），也称为淋巴细胞抗原 86（LY86），在 Toll 样受体 4（TLR4）信号通路中发挥重要作用。最近的研究表明，MD1 参与调节压力超负荷诱导的心脏结构和电重构。然而，MD1 对心肌缺血再灌注（I/R）损伤和 I/R 相关心律失常的影响尚不清楚。为了进一步研究这一点，本研究使用 MD1 敲除（MD1-KO）小鼠来研究 MD1 在调节心肌 I/R 损伤及其电生理学中的作用。结果表明，MD1 的缺失导致梗死面积增大，心脏损伤标志物活性增加，组织学损伤加重，心功能恶化，心肌 I/R 后生存率降低。同时，MD1 缺乏也加重了炎症反应，促进了心肌细胞凋亡，并增加了小鼠心肌 I/R 后室性心律失常的易感性。此外，MD1 的缺失增强了心肌 I/R 后 Toll 样受体 4（TLR4）/核因子 kappa B（NF-κB）信号通路的激活。因此，MD1 的缺失加剧了心肌 I/R 损伤，并增加了室性心律失常的易感性，这两者可能与 TLR4/NF-κB 信号通路的上调有关。
