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细胞外囊泡及其与代谢功能障碍相关脂肪性肝病实验模型中炎症因子的相关性。

Extracellular Vesicles and Their Correlation with Inflammatory Factors in an Experimental Model of Steatotic Liver Disease Associated with Metabolic Dysfunction.

机构信息

Graduate Program in Gastroenterology and Hepatology, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.

Experimental Laboratory of Hepatology and Gastroenterology, Center for Experimental Research, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.

出版信息

Metab Syndr Relat Disord. 2024 Jun;22(5):394-401. doi: 10.1089/met.2023.0284. Epub 2024 Mar 18.

Abstract

Extracellular vesicles (EVs) are promising as a biomarker of metabolic dysfunction associated steatotic liver disease (MASLD). The objective is to study EVs and their involvement in MASLD concerning the disease's pathogenesis and progression characteristics. Male adult Sprague Dawley rats were randomly assigned into two experimental models of MASLD: MASLD-16 and MASLD-28, animals received a choline-deficient high-fat diet (CHFD) and Control-16 and Control-28, animals received a standard diet (SD) for 16 and 28 weeks, respectively. Biological samples from these animal models were used, as well as previously registered variables. EVs from hepatic tissue were characterized using confocal microscopy. EVs were isolated through differential ultracentrifugation from serum and characterized using NanoSight. The data from the EVs were correlated with biochemical, molecular, and histopathological parameters. Liver EVs were identified through the flotillin-1 protein. EVs were isolated from the serum of all groups. There was a decrease of EVs concentration in MASLD-28 in comparison with Control-28 ( < 0.001) and a significant increase in EVs concentration in Control-28 compared with Control-16 ( < 0.001). There was a strong correlation between serum EVs concentration with hepatic gene expression of interleukin () ( = 0.685,  < 0.05), ( = 0.697,  < 0.05) and tumor necrosis factor-alpha (;  = 0.636,  < 0.05) in MASLD-16. Moreover, there was a strong correlation between serum EVs size and in MASLD-28 ( = 0.762,  < 0.05). The concentration and size of EVs correlated with inflammatory markers, suggesting their involvement in the systemic circulation, cellular communication, and development and progression of MASLD, demonstrating that EVs have the potential to serve as noninvasive biomarkers for MASLD diagnosis and prognosis.

摘要

细胞外囊泡(EVs)作为与代谢功能障碍相关的脂肪性肝病(MASLD)的生物标志物具有很大的潜力。本研究旨在探讨 EVs 及其在 MASLD 发病机制和进展特征中的作用。雄性成年 Sprague Dawley 大鼠被随机分为 MASLD 的两个实验模型:MASLD-16 和 MASLD-28,动物分别给予胆碱缺乏高脂饮食(CHFD)和对照-16 和对照-28,动物分别给予标准饮食(SD)16 和 28 周。使用这些动物模型的生物样本以及先前登记的变量。使用共聚焦显微镜对肝组织中的 EVs 进行特征描述。通过差速超速离心从血清中分离 EVs,并使用 NanoSight 进行特征描述。EVs 数据与生化、分子和组织病理学参数相关联。通过 flotillin-1 蛋白鉴定肝 EVs。从所有组的血清中分离 EVs。与对照-28 相比,MASLD-28 中的 EVs 浓度降低( < 0.001),而对照-28 中 EVs 浓度与对照-16 相比显著升高( < 0.001)。MASLD-16 中血清 EVs 浓度与肝基因表达的白细胞介素()( = 0.685,  < 0.05)、( = 0.697,  < 0.05)和肿瘤坏死因子-α(;  = 0.636,  < 0.05)之间存在很强的相关性。此外,MASLD-28 中血清 EVs 大小与 之间存在很强的相关性( = 0.762,  < 0.05)。EVs 的浓度和大小与炎症标志物相关,提示它们参与了全身循环、细胞通讯以及 MASLD 的发生和发展,表明 EVs 有可能作为 MASLD 诊断和预后的非侵入性生物标志物。

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