Programmed cell death-1 deficiency results in atrial remodeling in C57BL/6 mice
Programmed cell death-1 deficiency results in atrial remodeling in C57BL/6 mice
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程序性细胞死亡 1 缺陷导致 C57BL/6 小鼠心房重塑。
DOI：
10.3892/ijmm.2012.1218
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发表时间：
2013-02-01
影响因子：
5.4
通讯作者：
Zheng, Qiangsun
中科院分区：
文献类型：
--
作者：
Fu, Guoqiang;Cao, Yizhan;Zheng, Qiangsun
程序性细胞死亡-1（PD-1）基因的缺陷会增强T细胞活化并增加炎症水平。研究表明，心房颤动（AF）与炎症密切相关。本研究的目的是探讨PD-1缺陷在AF发病机制中的作用。实验中使用两组小鼠：C57 BL/6和C57 BL/6-PD-1（-/-）组。检测炎症细胞因子白细胞介素（IL）-2、-4、-6、-10、-17、干扰素-γ和肿瘤坏死因子的表达。同时测定心房肌细胞氧化应激水平、心房有效不应期（AERP）和心房肌纤维化水平。与C57 BL/6组相比，PD-1（-/-）组的炎症细胞因子明显升高，心房肌细胞氧化应激水平也明显升高。PD-1-/-组AERP缩短，离散度增加。此外，PD-1（-/-）组出现显著的心房心肌纤维化，但C57 BL/6组没有。我们的研究结果有力地表明，更高水平的炎症细胞因子和心房肌细胞氧化应激存在于PD-1（-/-）小鼠，并导致心房电和结构重构。由于心房重构，PD-1（-/-）小鼠更容易发生AF。
Deficiency of the programmed cell death-1 (PD-1) gene enhances T-cell activation and increases inflammation levels. It has been reported that atrial fibrillation (AF) is closely related to inflammation. The aim of the present study was to investigate the role of PD-1 deficiency in the pathogenesis of AF. Two groups of mice were used in our experiment: the C57BL/6 and the C57BL/6-PD-1(-/-) group. The expression of the inflammatory cytokines interleukin (IL)-2, -4, -6, -10, -17, interferon-gamma and tumor necrosis factor were detected. Furthermore, the levels of atrial myocyte oxidative stress, the atrial effective refractory period (AERP) and the atrial myocardial fibrosis levels were determined. Compared with the C57BL/6 group, we found that the inflammatory cytokines were significantly increased in the PD-1(-/-) group and the levels of atrial myocyte oxidative stress in the PD-1(-/-) group were also higher. The AERP became shorter and the dispersion of AERP was increased in the PD-1-/- group. Moreover, the PD-1(-/-) group presented significant atrial myocardial fibrosis but the C57BL/6 group did not. Our findings strongly suggest that the higher levels of inflammatory cytokines and atrial myocyte oxidative stress were present in the PD-1(-/-) mice and resulted in atrial electricity and structural remodeling. Due to the atrial remodeling, the PD-1(-/-) mice were more likely to develop AF.