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通过使用牛磺熊去氧胆酸(TUDCA)和 SCD 益生菌抑制 NLRP3 炎性小体来促进老年肝脏的长寿。

Promoting longevity in aged liver through NLRP3 inflammasome inhibition using tauroursodeoxycholic acid (TUDCA) and SCD probiotics.

机构信息

Department of Medical Biochemistry, Yüksek İhtisas University, Ankara, Turkey.

Department of Molecular Biology and Genetics, Muş Alparslan University Muş, Turkey; Department of Food Quality Control and Analysis, Muş Alparslan University Muş, Turkey.

出版信息

Arch Gerontol Geriatr. 2024 Oct;125:105517. doi: 10.1016/j.archger.2024.105517. Epub 2024 Jun 3.

DOI:10.1016/j.archger.2024.105517
PMID:38851091
Abstract

This investigation explores the combined influence of SCD Probiotics and tauroursodeoxycholic acid (TUDCA) on liver health in elderly male Sprague-Dawley rats. Through the administration of intravenous TUDCA (300 mg/kg) and oral SCD Probiotics (3 mL at 1 × 10^8 CFU) daily for one week, this study evaluates the biomolecular composition, histopathological alterations, and inflammasome activity in the liver. Analytical methods encompassed ATR-FTIR spectroscopy integrated with machine learning for the assessment of biomolecular structures, RT-qPCR for quantifying inflammasome markers (NLRP3, ASC, Caspase-1, IL18, IL1β), and histological examinations to assess liver pathology. The findings reveal that TUDCA prominently enhanced lipid metabolism by reducing cholesterol esters, while SCD Probiotics modulated both lipid and protein profiles, notably affecting fatty acid chain lengths and protein configurations. Histological analysis showed significant reductions in cellular degeneration, lymphatic infiltration, and hepatic fibrosis. Furthermore, the study noted a decrease in the immunoreactivity for NLRP3 and ASC, suggesting suppressed inflammasome activity. While SCD Probiotics reduced the expression of certain inflammasome-related genes, they also paradoxically increased AST and LDH levels. Conversely, an exclusive elevation in albumin levels was observed in the group treated with SCD Probiotics, implying a protective role against liver damage. These results underscore the therapeutic potential of TUDCA and SCD Probiotics for managing age-associated liver disorders, illustrating their individual and synergistic effects on liver health and pathology. This study provides insights into the complex interactions of these agents, advocating for customized therapeutic approaches to combat liver fibrosis, enhance liver functionality, and decrease inflammation in aging populations.

摘要

本研究旨在探讨 SCD 益生菌和牛磺熊去氧胆酸(TUDCA)联合对老年雄性 Sprague-Dawley 大鼠肝脏健康的影响。通过每周静脉注射 TUDCA(300mg/kg)和口服 SCD 益生菌(3mL,浓度为 1×10^8 CFU),评估了肝脏的生物分子组成、组织病理学改变和炎症小体活性。分析方法包括采用衰减全反射傅里叶变换红外光谱(ATR-FTIR)结合机器学习评估生物分子结构、实时定量聚合酶链式反应(RT-qPCR)定量炎症小体标志物(NLRP3、ASC、Caspase-1、IL18、IL1β)以及组织学检查评估肝脏病理学。结果表明,TUDCA 通过减少胆固醇酯显著增强了脂质代谢,而 SCD 益生菌则调节了脂质和蛋白质谱,特别是影响脂肪酸链长和蛋白质构象。组织学分析显示,细胞变性、淋巴浸润和肝纤维化显著减少。此外,研究还观察到 NLRP3 和 ASC 的免疫反应性降低,提示炎症小体活性受到抑制。虽然 SCD 益生菌降低了某些炎症小体相关基因的表达,但也出人意料地增加了 AST 和 LDH 水平。相反,仅在 SCD 益生菌治疗组中观察到白蛋白水平升高,表明其具有保护肝脏免受损伤的作用。这些结果突出了 TUDCA 和 SCD 益生菌在治疗与年龄相关的肝脏疾病方面的潜在疗效,表明它们对肝脏健康和病理学具有单独和协同作用。本研究深入探讨了这些药物的复杂相互作用,倡导针对特定人群制定治疗方案,以对抗肝纤维化、增强肝脏功能并减少老年人群的炎症。

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