5-羟甲基糠醛通过慢性炎症引起的细胞衰老相关肌肉减少症诱导小鼠虚弱。
5-Hydroxymethylfurfural induces mice frailty through cell senescence-associated sarcopenia caused by chronic inflammation.
作者信息
Xu Ting, Xia Rong, He Fan, Dong En-Hui, Shen Jie-Miao, Xu Chang-Chang, Ji Ming-Hui, Xu Qin
机构信息
School of Nursing, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, PR China.
Key Lab of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, 101 Longmian Avenue, Nanjing, 211166, PR China.
出版信息
Heliyon. 2023 Jan 22;9(2):e13217. doi: 10.1016/j.heliyon.2023.e13217. eCollection 2023 Feb.
OBJECTIVE
5-Hydroxymethylfurfural (5-HMF) is an important component of air pollution, confirmed to be a risk factor for pulmonary inflammation. However, its association with general health is unknown. This article aimed to clarify the effect and mechanism of 5-HMF in the occurrence and aggravation of frailty in mice by investigating whether exposure to 5-HMF was linked to the occurrence and aggravation of mice frailty.
METHODS
Twelve male C57BL/6 mice (12-month-old, 38 ± 1 g) were randomly divided into the control group and the 5-HMF group. The 5-HMF group was treated with 5-HMF (1 mg/kg/day, respiratory exposure) for 12 months, whereas the control group was treated with equal amounts of sterile water. After the intervention, the ELISA method was used to detect the serum inflammation level of the mice, and the physical performance and frail status were evaluated using a Fried physical phenotype-based assessment tool. The differences in the body compositions were calculated from their MRI images, and the pathological changes in their gastrocnemius muscle were revealed using the H&E staining. Furthermore, the senescence of skeletal muscle cells was evaluated by measuring the expression levels of senescence-related proteins by the western blotting.
RESULTS
In the 5-HMF group, serum inflammatory factors IL-6, TNF-α, and CRP levels were significantly raised ( < 0.01). Mice in this group had higher frailty scores and significantly reduced grip strength ( < 0.001), slower weight gains, less WVgastrocnemius muscle masses, and lower sarcopenia indices (SI). In addition, the cross-sectional areas of their skeletal muscles were reduced, and the levels of their cell senescence-related proteins (p53, p21, p16, SOD1, SOD2, SIRT1, SIRT3) were considerably altered ( < 0.01).
CONCLUSION
5-HMF may induce chronic and systemic inflammation, which in turn accelerates the progression of the frailty of mice through cell senescence.
目的
5-羟甲基糠醛（5-HMF）是空气污染的重要成分，已被证实是肺部炎症的危险因素。然而，其与总体健康的关联尚不清楚。本文旨在通过研究5-HMF暴露是否与小鼠虚弱的发生和加重有关，来阐明5-HMF在小鼠虚弱发生和加重过程中的作用及机制。
方法
将12只雄性C57BL/6小鼠（12月龄，体重38±1 g）随机分为对照组和5-HMF组。5-HMF组小鼠接受5-HMF（1 mg/kg/天，经呼吸道暴露）处理12个月，而对照组小鼠接受等量无菌水。干预后，采用酶联免疫吸附测定（ELISA）法检测小鼠血清炎症水平，并使用基于Fried身体表型的评估工具评估身体性能和虚弱状态。根据磁共振成像（MRI）图像计算身体成分差异，并使用苏木精-伊红（H&E）染色显示腓肠肌的病理变化。此外，通过蛋白质免疫印迹法测量衰老相关蛋白的表达水平，评估骨骼肌细胞的衰老情况。
结果
在5-HMF组中，血清炎症因子白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和C反应蛋白（CRP）水平显著升高（P<0.01）。该组小鼠的虚弱评分更高，握力显著降低（P<0.001），体重增加缓慢，腓肠肌质量的体重比更低，肌肉减少症指数（SI）更低。此外，其骨骼肌横截面积减小，细胞衰老相关蛋白（p53、p21、p16、超氧化物歧化酶1（SOD1）、超氧化物歧化酶2（SOD2）、沉默信息调节因子1（SIRT1）、沉默信息调节因子3（SIRT3））水平发生显著改变（P<0.01）。
结论
5-HMF可能诱导慢性全身性炎症，进而通过细胞衰老加速小鼠虚弱的进展。
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