膳食植物甾醇补充剂通过激活有丝分裂和调节肠道微生物群减轻肾脏纤维化。

IF 5.1 1区 农林科学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Food & Function Pub Date : 2025-02-24 DOI:10.1039/D4FO06043A
Fan Yang, Yingjie Gao, Siyi Xie, Wenjing Yang, Qiyan Wang, Wenqian Ye, Lu Sun, Jiangtao Zhou and XiuE Feng
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引用次数: 0

摘要

慢性肾脏疾病(CKD)是一项重大的全球健康挑战,主要由肾纤维化引起,治疗方案有限。解决这种情况需要有针对性的医疗或饮食干预。植物甾醇(PS)是存在于各种植物性食物中的类胆固醇生物活性化合物,具有抗氧化和抗炎作用。采用叶酸(FA)建立CKD小鼠模型,并添加两种PS:豆甾醇(Stig)和β-谷甾醇(β-Sito)。通过生化指标、病理、转录组学和16S rDNA测序研究了PS的作用和机制。结果表明,高剂量PS比低剂量PS和氯沙坦钾(LP)在减轻肾纤维化、恢复功能、调节氧化应激和炎症方面更有效,高剂量Stig和β-Sito治疗之间无显著差异。基因本体(Gene Ontology, GO)富集分析显示,PS在线粒体外膜、泛素-蛋白连接酶结合等细胞组分和分子过程相关通路中显著富集。PS降低TGF-β/Smad和cGAS/Sting1/TBK1的表达,激活PINK1/Parkin通路蛋白,从而减轻小鼠肾纤维化。慢性肾病通常与肠道菌群失衡和肠道屏障受损有关。我们的观察表明,PS恢复了肠道屏障,改变了肠道微生物群的组成,改善了CKD小鼠的肾功能。目前的研究结果表明,Stig和β-Sito都通过PINK1/Parkin途径激活线粒体自噬,调节肠道微生物群,从而减轻肾纤维化。该研究结果为开发PS补充剂在CKD管理中的有效应用提供了坚实而重要的意义,为研究和临床治疗提供了新的概念和方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Dietary phytosterol supplementation mitigates renal fibrosis via activating mitophagy and modulating the gut microbiota

Dietary phytosterol supplementation mitigates renal fibrosis via activating mitophagy and modulating the gut microbiota

Chronic kidney disease (CKD) poses a significant global health challenge, primarily driven by renal fibrosis, with limited treatment options. Addressing this condition necessitates either targeted medical treatments or dietary interventions. Phytosterols (PS) are cholesterol-like bioactive compounds in various plant-based foods with antioxidant and anti-inflammatory effects. A CKD mouse model was established using folic acid (FA) and treated with dietary supplements of two PS, stigmasterol (Stig) and β-sitosterol (β-Sito). The effects and mechanisms of PS were investigated through biochemical indices, pathology, transcriptomics, and 16S rDNA sequencing. The results indicated that high-dose PS are more effective than low-dose PS and Losartan potassium (LP) in reducing renal fibrosis, restoring function, and modulating oxidative stress and inflammation, with no significant differences between high-dose Stig and β-Sito treatments. Gene Ontology (GO) enrichment analysis revealed that PS were significantly enriched in pathways related to the mitochondrial outer membrane, ubiquitin-protein ligase binding, and other cellular components and molecular processes. PS reduced the expression of TGF-β/Smad and cGAS/Sting1/TBK1 and activated PINK1/Parkin pathway proteins, thereby mitigating renal fibrosis in mice. CKD is often associated with imbalanced gut microbiota and compromised intestinal barriers. Our observations indicated that PS restored the intestinal barrier, altered the composition of the gut microbiota, and improved renal function in CKD mice. The present findings indicate that both Stig and β-Sito activate mitophagy via the PINK1/Parkin pathway and modulate the gut microbiota, thereby alleviating renal fibrosis. The findings provide solid and significant implications for developing effective application of PS supplementation in the management of CKD, presenting novel concepts and approaches for research and clinical treatment.

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来源期刊
Food & Function
Food & Function BIOCHEMISTRY & MOLECULAR BIOLOGY-FOOD SCIENCE & TECHNOLOGY
CiteScore
10.10
自引率
6.60%
发文量
957
审稿时长
1.8 months
期刊介绍: Food & Function provides a unique venue for physicists, chemists, biochemists, nutritionists and other food scientists to publish work at the interface of the chemistry, physics and biology of food. The journal focuses on food and the functions of food in relation to health.
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