白藜芦醇降低ox-LDL诱导血小板ROS产生和PECAM-1表达的分子机制研究

摘要

Aim To investigate the effect of resveratrol on ROS level and PECAM-1 expression in ox-LDL-stimulated platelets. Methods The expression of PE-CAM-1 , Sirt1 and p38 MAPK phosphorylation in ox-LDL-stimulated platelets was determined by Western blot. The level of ROS was measured by immunofluo-rescence kit. Results ox-LDL induced platelet aggre-gation by 14%, whereas resveratrol inhibited platelet aggregation by 50%. Resveratrol decreased ROS level by 3 . 2 fold and completely suppressed PECAM-1 expression in ox-LDL-treated platelets. Resveratrol re-covered Sirt1 expression in ox-LDL-treated platelets. EX527 ( a Sirt1 inhibitor ) increased ROS level and PECAM-1 expression in ox-LDL-stimulated platelets. Meanwhile, resveratrol also suppressed p38MAPK phosphorylation induced by ox-LDL. Conclusion Resveratrol can inhibit platelet aggregation, decrease ROS production and PECAM-1 expression in ox-LDL-stimulated platelets. The mechanism maybe associated with recovery of Sirt1 expression. Moreover, resveratrol can decrease PECAM-1 expression, which may be linked to abolishing p38MAPK phosphorylation.%目的：探讨白藜芦醇对ox-LDL刺激血小板的ROS产生和PECAM-1表达的影响以及相关的分子机制。方法用ox-LDL刺激血小板,应用 Western blot 检测 PECAM-1、Sirt1的表达以及 p38MAPK的磷酸化。用荧光试剂盒检测 ROS水平。结果① ox-LDL刺激血小板时聚集率为14%,100μmol·L-1白藜芦醇抑制了血小板聚集,抑制率为50%。②白藜芦醇减少了ox-LDL诱导的ROS产生约3.2倍,并抑制了PECAM-1表达。③ ox-LDL 刺激血小板时 Sirt1表达降低,白藜芦醇(100μmol·L-1)逆转了这一现象。 Sirt1抑制剂EX527增加了血小板ROS水平和PECAM-1表达。④白藜芦醇抑制了ox-LDL刺激的p38MAPK磷酸化。结论白藜芦醇能够降低 ox-LDL 诱导的血小板聚集、抑制 ROS 产生,以及降低PECAM-1的表达,其分子机制与增加Sirt1的表达相关。此外,白藜芦醇抑制 PECAM-1表达与抑制p38MAPK磷酸化相关。