原儿茶醛对脂多糖损伤的血管内皮细胞的作用机制研究

Protection and related mechanisms of protocatechuic aldehyde against vascular endothelial cell injury induced by lipopolysaccharide

目的:研究复方丹参方中水溶性单体原儿茶醛对血管内皮细胞炎症反应的药理作用及机制。方法:使用脂多糖(LPS,0.5μg/m l)刺激人脐静脉内皮细胞,造成炎症模型,用原儿茶醛(0.25 mmol/L,0.5 mmol/L,1.0 mmol/L)加以干预;用RT-PCR和ELISA方法检测细胞间黏附分子-1和纤连蛋白的表达水平以及单核细胞趋化蛋白-1的分泌量;用W estern印迹方法观察了丝裂原激活的信号转导通路中ERK1/2、JNK和p38的活化情况。结果:原儿茶醛呈剂量依赖性地降低LPS导致的细胞间黏附分子-1及纤连蛋白的高表达,减少了单核细胞趋化蛋白-1的过度分泌,并能抑制ERK1/2、JNK和p38分子的活化。结论:原儿茶醛能通过抑制NF-κB-MAPK信号通路抑制脂多糖诱导的血管内皮细胞炎症反应。

Objective：To study the effect and related mechanism of protocatechuic aldehyde （PCA）, a major aqueous compound derived from a Chinese herb, Salvia miltiorrhiza, on inflammatory reaction of vascular endothelial cells, Methods： Human umbilical vein endothelial cells were cultured with PCA （mmol/L,0.25,0.5 or 1.0, 12 h）, followed by stimulation with lipopolysaccharide （ LPS, 0. 5 μg/ml, 12 h ） . The expression of intercellular adhesion molecule-1 （ICAM-1） , fibronectin （FN） and the secretion of monocyte chemoattractant protein-1 （ MCP-1 ） were detected by ELISA assay. Western blot assay was used to study the activity of ERK1/2, JNK and p38 mitogen-activated protein kinases （MAPKs）. Results：PCA dose-dependently inhibied LPS up-regulated ICAM-1 and FN as well as the secretion of MCP-1. The activities of ERK1/2, JNK and p38 MAPKs were down-regulated by PCA in a dose-dependent manner. Conclusion： These results suggest that PCA can protect vascular endothelial cells against LPS stimulation by inhibition of inflammation via MAPK pathway.