关键词: ATR-FTIR Fibrosis Inflammation Liver NLRP3 inflammasome SCD Probiotics TUDCA

Mesh : Animals Taurochenodeoxycholic Acid / pharmacology NLR Family, Pyrin Domain-Containing 3 Protein / metabolism Probiotics / pharmacology therapeutic use Male Rats Rats, Sprague-Dawley Inflammasomes / metabolism drug effects Liver / pathology drug effects metabolism Longevity / drug effects Lipid Metabolism / drug effects Aging / drug effects

来  源:   DOI:10.1016/j.archger.2024.105517

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:
这项研究探讨了SCD益生菌和牛磺熊去氧胆酸(TUDCA)对老年雄性Sprague-Dawley大鼠肝脏健康的联合影响。通过每天静脉注射TUDCA(300mg/kg)和口服SCD益生菌(3mL,1×10^8CFU),持续一周,这项研究评估了生物分子的组成,组织病理学改变,和肝脏中的炎性体活性。分析方法包括ATR-FTIR光谱与机器学习相结合,用于评估生物分子结构。RT-qPCR定量炎性体标志物(NLRP3,ASC,Caspase-1,IL18,IL1β),和组织学检查以评估肝脏病理。研究结果表明,TUDCA通过减少胆固醇酯显著增强脂质代谢,虽然SCD益生菌调节脂质和蛋白质谱,显著影响脂肪酸链长度和蛋白质构型。组织学分析显示细胞变性显著减少,淋巴浸润,和肝纤维化。此外,该研究注意到NLRP3和ASC的免疫反应性降低,提示炎症小体活动受到抑制。虽然SCD益生菌降低了某些炎症相关基因的表达,它们还矛盾地增加了AST和LDH水平。相反,在接受SCD益生菌治疗的组中观察到白蛋白水平的唯一升高,暗示着对肝脏损伤的保护作用。这些结果强调了TUDCA和SCD益生菌治疗年龄相关性肝脏疾病的潜力,说明他们对肝脏健康和病理的个体和协同作用。这项研究提供了对这些代理的复杂相互作用的见解,倡导定制治疗方法来对抗肝纤维化,增强肝脏功能,减少衰老人群的炎症。
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