Dong Xiaowu, Luo Weiwei, Wang Yaodong, Zhu Qingtian, Yuan Chenchen, Xiao Weiming, Gong Weijuan, Lu Guotao, Shi Xiaolei, Li Jin
Pancreatic Center, Department of Gastroenterology, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, China.
Department of Gastroenterology, Kunshan Hospital of Traditional Chinese Medicine, Affiliated Hospital of Yangzhou University, Kunshan, Jiangsu, China.
Skelet Muscle. 2024 Dec 3;14(1):29. doi: 10.1186/s13395-024-00363-1.
Severe acute pancreatitis (SAP) is characterized by high mortality rates and various complications, including skeletal muscle atrophy, which significantly exacerbates its outcomes. Despite its clinical relevance, the mechanistic understanding of the relationship between skeletal muscle and the pancreas in SAP remains limited. Our study aimed to elucidate this "organ crosstalk" and its potential implications.
We established an SAP mouse model through pancreatic duct ligation (PDL) and evaluated pancreatic necrosis, skeletal muscle atrophy, and myonectin expression levels. Recombinant myonectin protein was administered in vivo and in vitro to assess its effects on acinar cell necrosis. Mechanistic insights were gained through RNA-seq data analysis and experimental validation. Serum samples from AP patients and healthy controls were collected to investigate the correlation between serum myonectin levels and disease severity.
The mouse model exhibited severe pancreatic necrosis, skeletal muscle atrophy, and elevated myonectin levels, with myonectin administration exacerbating model severity. We identified iron accumulation-induced ferroptosis as a key pathway contributing to myonectin-mediated acinar cell necrosis. A total of 22 healthy controls and 52 patients with varying degrees of AP were included in the serum samples and clinical data (36.5% females, age 49.79 ± 16.53). Analysis of serum samples revealed significantly higher myonectin levels in AP patients, correlating with disease severity (R = 0.28, P = 0.041).
Our findings underscore the significant role of myonectin in SAP progression and its potential as a prognostic marker for disease severity in AP patients. This study contributes to a deeper understanding of the pathophysiology of SAP and highlights potential therapeutic targets for intervention.
重症急性胰腺炎（SAP）的特点是死亡率高且伴有各种并发症，包括骨骼肌萎缩，这显著加重了其病情结局。尽管其具有临床相关性，但对SAP中骨骼肌与胰腺之间关系的机制理解仍然有限。我们的研究旨在阐明这种“器官间相互作用”及其潜在影响。
我们通过胰管结扎（PDL）建立了SAP小鼠模型，并评估胰腺坏死、骨骼肌萎缩和肌连接蛋白表达水平。在体内和体外给予重组肌连接蛋白蛋白以评估其对腺泡细胞坏死的影响。通过RNA测序数据分析和实验验证获得机制性见解。收集急性胰腺炎（AP）患者和健康对照者的血清样本，以研究血清肌连接蛋白水平与疾病严重程度之间的相关性。
小鼠模型表现出严重的胰腺坏死、骨骼肌萎缩和肌连接蛋白水平升高，给予肌连接蛋白会加重模型的严重程度。我们确定铁积累诱导的铁死亡是导致肌连接蛋白介导的腺泡细胞坏死的关键途径。血清样本和临床数据纳入了22名健康对照者和52名不同程度AP患者（女性占36.5%，年龄49.79±16.53）。血清样本分析显示，AP患者的肌连接蛋白水平显著更高，与疾病严重程度相关（R = 0.28，P = 0.041）。
我们的研究结果强调了肌连接蛋白在SAP进展中的重要作用及其作为AP患者疾病严重程度预后标志物的潜力。本研究有助于更深入地理解SAP的病理生理学，并突出了潜在的干预治疗靶点。
