西利马林通过在氧化LDL暴露的内皮细胞中调节Erk-5来预防内皮功能障碍,防止内皮功能障碍
Rohit Patel1, Sanjay Kumar2, Johnna F Varghese1
1Metabolic Disorders and Inflammatory Pathologies Laboratory, School of Life Sciences, Central University of Gujarat, Gandhinagar, Gujarat 382030, India; Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Microvascular research
|February 2, 2024
概括
西利马林 (Sym) 通过增加Erk-5水平和保护内皮细胞标记物,保护内皮功能障碍 (ED). 这种天然化合物在高脂肪饮食诱导的肥胖模型中显示出有望预防动脉样硬化.
科学领域:
- 心血管生物学 心血管生物学
- 内皮细胞生物学 内皮细胞生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 内皮功能障碍 (ED) 与内皮细胞平衡受损有关,通常由细胞外信号调节激酶 (Erk) -5介导.
- 氧化低密度脂蛋白 (oxLDL) 是ED和动脉样硬化发展的关键因素,特别是在代谢障碍中.
- 西利玛林 (Sym),一种植物衍生的黄,已证明具有药理上的益处,但其在预防ED方面的特殊作用需要阐明.
研究的目的:
- 研究西利马林 (Sym) 对Erk-5表达的作用及其改善内皮功能障碍 (ED) 的潜力.
- 为了评估Sym在体外和高脂肪饮食 (HFD) 诱导的肥胖模型中对oxLDL诱导的内皮损伤的保护机制.
主要方法:
- 在体外研究中使用了人类静脉内皮细胞 (pHUVECs) 来评估活力 (MTT检测),基因/蛋白质表达 (RT-qPCR,西方斑点) 和管形成.
- 在体内实验中,小鼠在正常或HFD状态下服用Sym或Erk-5抑制剂,监测体重,血糖,脂质样本 (LDL,oxLDL) 和大动脉内皮细胞标志物表达.
主要成果:
- 在oxLDL暴露下,西利马林 (5微克/毫升) 保持了pHUVEC活力和管形成能力.
- 在oxLDL处理的pHUVEC中,Sym对Erk-5,von Willebrand因子 (vWF) 和内皮氧化合成酶 (eNOS) 进行上调,同时对细胞间粘附分子-1 (ICAM-1) 进行下调.
- 在HFD养的小鼠中,Sym降低了体重,血糖,LDL胆固醇和oxLDL水平,同时增加了大动脉Erk-5,vWF和eNOS,并降低了ICAM-1.
结论:
- 西利马林通过提高内皮细胞中的Erk-5水平,显示出作为抗动脉样硬化剂的显著潜力.
- Sym有效地预防由氧化LDL引起的内皮功能障碍,特别是在HFD引起的肥胖症的背景下.
- 这些发现强调了西利马林在治疗与动脉样硬化和内皮功能障碍相关的代谢障碍方面的治疗价值.
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