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飞燕草素通过 ROS/p38MAPK/NF-κB 通路抑制氧化型低密度脂蛋白诱导的单核细胞-内皮细胞黏附。

Inhibitory effect of delphinidin on monocyte-endothelial cell adhesion induced by oxidized low-density lipoprotein via ROS/p38MAPK/NF-κB pathway.

机构信息

Research Center of Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, The Third Military Medical University, Chongqing, People's Republic of China.

出版信息

Cell Biochem Biophys. 2011 Nov;61(2):337-48. doi: 10.1007/s12013-011-9216-2.

DOI:10.1007/s12013-011-9216-2
PMID:21695376
Abstract

Monocyte adhesion to the vascular endothelium and their subsequent trans-endothelial migration are pivotal early events in atherogenesis. In this study, the effect of delphinidin, belonging to the group of anthocyanin, on adhesion of monocytes to endothelial cells induced by ox-LDL was investigated. The results showed that the pre-treatment with delphinidin (50, 100, or 200 μM) dose-dependently decreased the ox-LDL-induced up-regulation of the expression of ICAM-1 and P-selectin, and the enhanced adhesion and transmigration of monocytes. To determine the role of ROS/p38MAPK/NF-κB pathway, intracellular ROS level, p38MAPK protein expression, NF-κB transcription activity and protein expression, IκB-α degradation, NADPH oxidase subunit (Nox2 and p22phox) protein, and mRNA expression were measured. The results showed that delphinidin attenuated ox-LDL-induced generation of ROS, p38MAPK protein expression, NF-κB transcription activity and protein expression, IκB-α degradation, NADPH oxidase subunit (Nox2 and p22phox) protein and mRNA expression in endothelial cells in a dose-dependent manner. These results suggest that delphinidin attenuates ox-LDL induced expression of adhesion molecules (P-selectin and ICAM-1) and the adhesion of monocytes to endothelial cells by inhibiting ROS/p38MAPK/NF-κB pathway. These findings provide a basis for the design of potent antiatherosclerotic agents that will have therapeutic potential in the prevention of AS.

摘要

单核细胞黏附于血管内皮细胞并随后穿过内皮细胞迁移是动脉粥样硬化形成过程中的早期关键事件。在这项研究中,研究了属于花色苷类的飞燕草素对 ox-LDL 诱导的单核细胞黏附于内皮细胞的影响。结果表明,飞燕草素(50、100 或 200μM)预处理可剂量依赖性地降低 ox-LDL 诱导的 ICAM-1 和 P-选择素表达上调,以及单核细胞黏附和迁移增强。为了确定 ROS/p38MAPK/NF-κB 通路的作用,测量了细胞内 ROS 水平、p38MAPK 蛋白表达、NF-κB 转录活性和蛋白表达、IκB-α 降解、NADPH 氧化酶亚基(Nox2 和 p22phox)蛋白和 mRNA 表达。结果表明,飞燕草素可剂量依赖性地减弱 ox-LDL 诱导的 ROS 生成、p38MAPK 蛋白表达、NF-κB 转录活性和蛋白表达、IκB-α 降解、NADPH 氧化酶亚基(Nox2 和 p22phox)蛋白和 mRNA 表达。这些结果表明,飞燕草素通过抑制 ROS/p38MAPK/NF-κB 通路减弱 ox-LDL 诱导的黏附分子(P-选择素和 ICAM-1)表达和单核细胞与内皮细胞的黏附。这些发现为设计具有抗动脉粥样硬化作用的有效药物提供了依据,这些药物可能具有预防 AS 的治疗潜力。

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