Bai Xinyue, Zhang Wanting, Zhang Yingyue, Xu Xin
School of Exercise and Health, Shanghai University of Sport, Shanghai, China.
Research Institute for Doping Control, Shanghai University of Sport, Shanghai, China.
PLoS One. 2025 Aug 22;20(8):e0329973. doi: 10.1371/journal.pone.0329973. eCollection 2025.
Downhill running (DR) has recently emerged as a promising exercise modality for cardiac rehabilitation, but the effect and mechanism of DR on myocardium remains unclear. General control nonderepressible 2 (GCN2), an eukaryotic initiation factor 2α (eIF2α) kinase, is beneficial to the heart when it is deficiency. The current study aimed to explore whether the GCN2 is associated with cardioprotective effects in downhill running. Eight-week-old male wild type (WT) mice and GCN2 knock out (KO) mice were randomly divided into WT control (n = 6), WT exercise(n = 5), GCN2 KO control(n = 5), and GCN2 KO exercise(n = 5) groups. Mice in the exercise groups were subjected to a single session of downhill running treadmill exercise training. In WT mice, DR increased the proportion of basophils, decreased the percentage of lymphocytes in the blood, and decreased the expression of GCN2, Ifn-γ, Tgf-βr1 and immune cell markers in the myocardium. Compared with WT mice, GCN2 KO mice decreased the proportion of monocytes and neutrophils in the blood, decreased expression of Ifn-γ, Tgf-βr1 and immune cell markers, and increased expression of Il-12α in the myocardium. In GCN2 KO mice, DR increased the expression of immune cell markers in the myocardium. DR and GCN2 KO both reduced TGF-β1 expression, and elevated p-eif2a expression in the myocardium. This finding demonstrated that downhill running alters inflammation and immune response in the myocardium, which is associated with GCN2.
下坡跑（DR）最近已成为心脏康复中一种很有前景的运动方式，但DR对心肌的影响和机制仍不清楚。一般控制非抑制性2（GCN2）是一种真核起始因子2α（eIF2α）激酶，当其缺乏时对心脏有益。本研究旨在探讨GCN2是否与下坡跑中的心脏保护作用相关。将8周龄雄性野生型（WT）小鼠和GCN2基因敲除（KO）小鼠随机分为WT对照组（n = 6）、WT运动组（n = 5）、GCN2 KO对照组（n = 5）和GCN2 KO运动组（n = 5）。运动组的小鼠进行单次下坡跑跑步机运动训练。在WT小鼠中，DR增加了嗜碱性粒细胞的比例，降低了血液中淋巴细胞的百分比，并降低了心肌中GCN2、Ifn-γ、Tgf-βr1和免疫细胞标志物的表达。与WT小鼠相比，GCN2 KO小鼠降低了血液中单核细胞和中性粒细胞的比例，降低了Ifn-γ、Tgf-βr1和免疫细胞标志物的表达，并增加了心肌中Il-12α的表达。在GCN2 KO小鼠中，DR增加了心肌中免疫细胞标志物的表达。DR和GCN2 KO均降低了心肌中TGF-β1的表达，并提高了p-eif2a的表达。这一发现表明，下坡跑会改变心肌中的炎症和免疫反应，这与GCN2有关。
