School of Public Health, Bengbu Medical University, Bengbu 233030, PR China.
Bengbu Medical University Key Laboratory of Cancer Research and Clinical Laboratory Diagnosis, Department of Biochemistry and Molecular Biology, School of Laboratory Medicine, Bengbu Medical University, Bengbu 233030, PR China.
Phytomedicine. 2024 Dec;135:156058. doi: 10.1016/j.phymed.2024.156058. Epub 2024 Sep 16.
Changes in modern lifestyles have led to an increase in obesity rates. Excessive lipid accumulation leads to abnormal cholesterol metabolism, and maintaining a balanced cholesterol metabolism is essential for the normal functioning of cells and the body. Rutin belongs to the group of flavonoids with hypolipidemic, anti-inflammatory and antioxidant effects. The aim of this study was to investigate the role of rutin in cholesterol metabolism disorders induced by a high cholesterol diet in zebrafish larvae. The trial was divided into five groups: Normal diet (ND), 5 % high cholesterol diet (HCD), 5 % high cholesterol diet with 80 μg/g ezetimibe diet (EZE), 5 % high cholesterol diet with 5 % rutin diet (RL-HCD), and 5 % high cholesterol diet with 10 % rutin diet (RH-HCD). Zebrafish larvae at 5 dpf were randomly divided into five groups and continuously fed different diets for 10 days, after 10 days zebrafish samples were collected for subsequent experiments. Body length, body width, oil red O, and Nile red staining were measured to detect biochemical indexes, analyze inflammatory response and lipid accumulation. Vascular endothelial injury was assessed by stereofluorescence microscopy and ELISA. In order to study the protective effect of rutin in zebrafish with cholesterol metabolism disorder induced by HCD, RNA-seq and LC-MS/MS nontargeted metabolomics were employed. The results indicate that HCD led to an increase in the body length and width of zebrafish. The HCD group induced an increase in body length and width, lipid accumulation, and exacerbated inflammation. Additionally, vascular damage and abnormal expression of endothelial cell markers were observed. Rutin lowered lipid levels in zebrafish fed an HCD, reduced inflammation, and protected endothelial cells. The RNA-seq and metabolomic analysis combined demonstrated that rutin effectively ameliorates the disorder of cholesterol metabolism in vivo by reducing cholesterol synthesis and promoting cholesterol transport.
现代生活方式的改变导致肥胖率上升。过量的脂质积累导致胆固醇代谢异常，维持胆固醇代谢平衡对于细胞和身体的正常功能至关重要。芦丁属于黄酮类化合物，具有降血脂、抗炎和抗氧化作用。本研究旨在探讨芦丁在高胆固醇饮食诱导的斑马鱼幼虫胆固醇代谢紊乱中的作用。试验分为五组：正常饮食（ND）、5%高胆固醇饮食（HCD）、5%高胆固醇饮食+80μg/g 依折麦布饮食（EZE）、5%高胆固醇饮食+5%芦丁饮食（RL-HCD）和 5%高胆固醇饮食+10%芦丁饮食（RH-HCD）。5dpf 的斑马鱼幼鱼随机分为五组，连续喂食不同饮食 10 天，10 天后收集斑马鱼样本进行后续实验。测量体长、体宽、油红 O 和尼罗红染色，以检测生化指标，分析炎症反应和脂质积累。通过立体荧光显微镜和 ELISA 评估血管内皮损伤。为了研究芦丁对 HCD 诱导的斑马鱼胆固醇代谢紊乱的保护作用，采用 RNA-seq 和 LC-MS/MS 非靶向代谢组学进行研究。结果表明，HCD 导致斑马鱼体长和体宽增加。HCD 组诱导体长和体宽增加、脂质积累增加，并加重炎症。此外，还观察到血管损伤和内皮细胞标志物表达异常。芦丁降低了 HCD 喂养的斑马鱼的脂质水平，减轻了炎症，并保护了内皮细胞。RNA-seq 和代谢组学分析联合表明，芦丁通过降低胆固醇合成和促进胆固醇转运，有效改善体内胆固醇代谢紊乱。
