Loss of MD1 exacerbates myocardial ischemia/reperfusion injury and susceptibility to ventricular arrhythmia
Loss of MD1 exacerbates myocardial ischemia/reperfusion injury and susceptibility to ventricular arrhythmia
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DOI：
10.1016/j.ejphar.2018.11.025
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发表时间：
2019-02-05
影响因子：
5
通讯作者：
Huang, He
中科院分区：
文献类型：
--
作者：
Jiang, Xiaobo;Kong, Bin;Huang, He
髓样分化蛋白1（MD 1），也称为淋巴细胞抗原86（LY 86），在Toll样受体4（TLR 4）信号通路中起重要作用。最近的研究表明，MD 1参与调节压力超负荷诱导的心脏结构和电重构。然而，MD 1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MD 1基因敲除小鼠心肌缺血再灌注损伤的机制，本研究采用MD 1基因敲除小鼠，研究MD 1基因在心肌缺血再灌注损伤中的作用及其电生理机制。结果表明，心肌I/R后MD 1的缺失导致心肌梗死面积增大，心肌损伤标志物活性增高，组织学损害加重，心功能恶化，存活率降低。同时，MD 1缺陷还加重了心肌I/R小鼠的炎症反应，促进了心肌细胞凋亡，增加了室性心律失常的易感性。此外，MD 1的缺失增强了心肌I/R后Toll样受体4（TLR 4）/核因子κ B（NF-κ B）信号通路的激活。因此，MD 1的缺失加重了心肌I/R损伤，增加了室性心律失常的易感性，二者可能与TLR 4/NF-κ B信号通路的上调有关。
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-kappa B) 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-kappa B signaling pathway.