Department of Trauma, Orthopedics and Reconstructive Surgery, Georg-August-University of Göttingen, Göttingen, Germany.
Department of General, Visceral and Pediatric Surgery, University Medical Center Göttingen, Göttingen, Germany.
Inflamm Bowel Dis. 2020 Jan 1;26(1):56-65. doi: 10.1093/ibd/izz127.
Recent studies implicate that 42% of inflammatory bowel disease (IBD) patients suffer from sarcopenia, the loss of muscle mass and strength, increasing the risk of falls and fall-related injuries. To determine the impact and molecular basis of IBD-associated sarcopenia, we sought to establish and characterize an experimental model for IBD-associated sarcopenia in vivo.
To induce colitis, male mice were treated with 0.75% dextran sodium sulfate (DSS) over a period of 14 days. Upon sacrifice, colon length and epithelial damage were determined to test local inflammation, and bone fragility was used as an indication for systemic inflammation. Muscle weight was measured, and morphology and fiber type distribution were assessed histologically. The molecular basis of sarcopenia was tested in M. quadriceps using qRT-PCR and by measuring the total protein content.
The overall weight of Mm. quadriceps and gastrocnemius was reduced, and the muscle damage marker creatine kinase was slightly elevated upon DSS treatment. The successful induction of sarcopenia was further supported by the decrease in muscle fiber size, affecting both type 1 and 2 fibers. Moreover, these muscles displayed increased mRNA expression of the E3 ligases MuRF1 and Atrogin1/MAFbx, and accordingly, the overall protein content was reduced.
Our findings demonstrate that DSS-induced colitis leads to severe muscle loss in mice and therefore is a suitable model to induce inflammation-associated sarcopenia.
最近的研究表明，42%的炎症性肠病（IBD）患者患有肌肉减少症，即肌肉质量和力量的丧失，这增加了跌倒和与跌倒相关的伤害的风险。为了确定 IBD 相关肌肉减少症的影响和分子基础，我们试图在体内建立和描述 IBD 相关肌肉减少症的实验模型。
为了诱导结肠炎，雄性小鼠接受了为期 14 天的 0.75%葡聚糖硫酸钠（DSS）处理。在处死时，测量结肠长度和上皮损伤以测试局部炎症，并且骨脆性用作全身炎症的指标。测量肌肉重量，并通过组织学评估形态和纤维类型分布。使用 qRT-PCR 和测量总蛋白含量来测试 M.quadriceps 中的肌肉减少症的分子基础。
Mm.quadriceps 和腓肠肌的总重量减轻，并且 DSS 处理后肌酸激酶等肌肉损伤标志物略有升高。肌肉纤维大小的减少进一步支持了肌肉减少症的成功诱导，这影响了 1 型和 2 型纤维。此外，这些肌肉显示出 E3 连接酶 MuRF1 和 Atrogin1/MAFbx 的 mRNA 表达增加，并且相应地，总蛋白含量降低。
我们的研究结果表明，DSS 诱导的结肠炎导致小鼠严重的肌肉损失，因此是诱导炎症相关肌肉减少症的合适模型。
