Huber Yvonne, Gehrke Nadine, Biedenbach Jana, Helmig Susanne, Simon Perikles, Straub Beate K, Bergheim Ina, Huber Tobias, Schuppan Detlef, Galle Peter R, Wörns Marcus A, Schuchmann Marcus, Schattenberg Jörn M
I. Department of Medicine, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.
Department of Sports Medicine, Rehabilitation and Prevention, Johannes Gutenberg University, Mainz, Germany.
Cell Death Dis. 2017 Jun 22;8(6):e2893. doi: 10.1038/cddis.2017.266.
Physical activity confers a broad spectrum of health benefits. Beyond the obvious role in metabolically driven diseases, the role of physical activity in acute liver injury is poorly explored. To study the role of physical activity in acute liver injury, a novel model of voluntary distance running in mice was developed and mice were subjected to acute liver injury induced by N-galactosamine (GalN) and lipopolysaccharide (LPS). Analyses included histological stains, immunoblotting, qRT-PCR and FACS analysis. Voluntary distance running increased to an average of 10.3 km/day after a learning curve. Running lead to a decrease in the absolute numbers of intrahepatic CD4+ T and B lymphocytes and macrophages after 7 weeks. In parallel, hepatic mRNA expression of inflammatory cytokines including IL-6 and IL-1beta, TGF-beta and monocyte chemoattractant protein-1 (MCP-1/CCL2) were suppressed, while TNF-α was not affected by exercise. Likewise, expression of the macrophage-specific antigen F4/80 was downregulated 1.6-fold from exercise. Notably, acute liver injury from GaIN/LPS was significantly blunted following 7 weeks of voluntary exercise as determined by liver histology, a 84.6% reduction of alanine aminotransferase (P<0.01) and a 54.6% reduction of aspartate aminotransferase (P<0.05) compared with sedentary mice. Additionally, proinflammatory cytokines, activation of caspase 3 and JNK were significantly lower, while antiapoptotic protein A20 increased. Voluntary distance running alters the intrahepatic immune phenotype producing an environment that is less susceptible to acute liver injury.
体育活动对健康有广泛益处。除了在代谢性疾病中发挥的明显作用外，体育活动在急性肝损伤中的作用鲜有研究。为了研究体育活动在急性肝损伤中的作用，我们建立了一种新的小鼠自愿长跑模型，并使小鼠遭受N-半乳糖胺（GalN）和脂多糖（LPS）诱导的急性肝损伤。分析包括组织学染色、免疫印迹、qRT-PCR和流式细胞术分析。经过学习曲线后，小鼠自愿长跑平均增加到每天10.3公里。7周后，长跑导致肝内CD4+T淋巴细胞、B淋巴细胞和巨噬细胞的绝对数量减少。同时，包括IL-6和IL-1β、TGF-β和单核细胞趋化蛋白-1（MCP-1/CCL2）在内的炎性细胞因子的肝mRNA表达受到抑制，而TNF-α不受运动影响。同样，运动使巨噬细胞特异性抗原F4/80的表达下调了1.6倍。值得注意的是，通过肝脏组织学检查发现，经过7周的自愿运动后，GalN/LPS引起的急性肝损伤明显减轻，与久坐不动的小鼠相比，丙氨酸转氨酶降低了84.6%（P<0.01），天冬氨酸转氨酶降低了54.6%（P<0.05）。此外，促炎细胞因子、caspase 3和JNK的激活显著降低，而抗凋亡蛋白A20增加。自愿长跑改变了肝内免疫表型，产生了一个对急性肝损伤不太敏感的环境。
