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芦丁通过诱导自噬和调节 PI3K/AKT 信号通路抑制氧化型低密度脂蛋白诱导的巨噬细胞炎症和泡沫细胞形成。

Rutin Inhibits Ox-LDL-Mediated Macrophage Inflammation and Foam Cell Formation by Inducing Autophagy and Modulating PI3K/ATK Signaling.

机构信息

Department of Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China.

The First Clinical School of Medicine, Nanjing Medical University, Nanjing 210000, China.

出版信息

Molecules. 2022 Jun 29;27(13):4201. doi: 10.3390/molecules27134201.

Abstract

Atherosclerosis (AS) is one of the leading causes of death among the elderly, and is primarily caused by foam cell generation and macrophage inflammation. Rutin is an anti-inflammatory, anti-oxidant, anti-allergic, and antiviral flavonoid molecule, known to have anti-atherosclerotic and autophagy-inducing properties, but its biological mechanism remains poorly understood. In this study, we uncovered that rutin could suppress the generation of inflammatory factors and reactive oxygen species (ROS) in ox-LDL-induced M2 macrophages and enhance their polarization. Moreover, rutin could decrease foam cell production, as shown by oil red O staining. In addition, rutin could increase the number of autophagosomes and the LC3II/I ratio, while lowering p62 expression. Furthermore, rutin could significantly inhibit the PI3K/ATK signaling pathway. In summary, rutin inhibits ox-LDL-mediated macrophage inflammation and foam cell formation by inducing autophagy and modulating PI3K/ATK signaling, showing potential in treating atherosclerosis.

摘要

动脉粥样硬化(AS)是老年人死亡的主要原因之一,主要由泡沫细胞生成和巨噬细胞炎症引起。芦丁是一种具有抗炎、抗氧化、抗过敏和抗病毒作用的类黄酮分子,已知具有抗动脉粥样硬化和诱导自噬的特性,但它的生物学机制仍不清楚。在这项研究中,我们发现芦丁可以抑制 ox-LDL 诱导的 M2 巨噬细胞中炎症因子和活性氧(ROS)的生成,并增强其极化。此外,芦丁可以减少泡沫细胞的生成,如油红 O 染色所示。此外,芦丁可以增加自噬体的数量和 LC3II/I 比值,同时降低 p62 的表达。此外,芦丁可以显著抑制 PI3K/ATK 信号通路。总之,芦丁通过诱导自噬和调节 PI3K/ATK 信号通路抑制 ox-LDL 介导的巨噬细胞炎症和泡沫细胞形成,显示出在治疗动脉粥样硬化方面的潜力。

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