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利用患有慢性胰腺炎的猪模型理解青年人群中继发性肌肉减少症的发展。

Understanding Secondary Sarcopenia Development in Young Adults Using Pig Model with Chronic Pancreatitis.

机构信息

Department of Animal Physiology, Faculty of Veterinary Medicine, University of Life Sciences in Lublin, 20-950 Lublin, Poland.

Department of Animal Genetics, Breeding and Ethology, Faculty of Animal Sciences, University of Agriculture in Kraków, 30-059 Kraków, Poland.

出版信息

Int J Mol Sci. 2024 Aug 10;25(16):8735. doi: 10.3390/ijms25168735.

Abstract

Chronic pancreatitis (CP) in young individuals may lead to disease-related secondary sarcopenia (SSARC), characterized by muscle loss and systemic inflammation. In this study, CP was induced in young pigs, and serum levels of key hormones, muscle fiber diameters in various muscles, and the mRNA expression of genes related to oxidative stress and programmed cell death were assessed. A decrease in muscle fiber diameters was observed in SSARC pigs, particularly in the longissimus and diaphragm muscles. Hormonal analysis revealed alterations in dehydroepiandrosterone, testosterone, oxytocin, myostatin, and cortisol levels, indicating a distinct hormonal response in SSARC pigs compared to controls. Oxytocin levels in SSARC pigs were significantly lower and myostatin levels higher. Additionally, changes in the expression of catalase (), caspase 8 (CASP8), B-cell lymphoma 2 (), and BCL2-associated X protein () mRNA suggested a downregulation of oxidative stress response and apoptosis regulation. A reduced / ratio in SSARC pigs implied potential caspase-independent cell death pathways. The findings highlight the complex interplay between hormonal changes and muscle degradation in SSARC, underscoring the need for further research into the apoptotic and inflammatory pathways involved in muscle changes due to chronic organ inflammation in young individuals.

摘要

慢性胰腺炎(CP)在年轻人中可能导致与疾病相关的继发性肌肉减少症(SSARC),其特征是肌肉减少和全身炎症。在这项研究中,诱导年轻猪发生 CP,并评估血清中关键激素水平、各种肌肉中的肌纤维直径以及与氧化应激和程序性细胞死亡相关的基因的 mRNA 表达。在 SSARC 猪中观察到肌纤维直径减小,尤其是在最长肌和膈肌中。激素分析显示脱氢表雄酮、睾丸激素、催产素、肌肉生长抑制素和皮质醇水平发生变化,表明 SSARC 猪与对照组相比存在明显的激素反应。SSARC 猪的催产素水平明显降低,肌肉生长抑制素水平升高。此外,过氧化氢酶 ()、半胱天冬酶 8 (CASP8)、B 细胞淋巴瘤 2 () 和 BCL2 相关 X 蛋白 () mRNA 的表达变化表明氧化应激反应和细胞凋亡调节的下调。SSARC 猪中 / 比值降低表明潜在的半胱天冬酶非依赖性细胞死亡途径。这些发现强调了 SSARC 中激素变化和肌肉降解之间的复杂相互作用,突出了需要进一步研究由于年轻人慢性器官炎症导致的肌肉变化涉及的细胞凋亡和炎症途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bc25/11354544/86c1fbea9b7f/ijms-25-08735-g001.jpg

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