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作 者:孙杰[1] 孙文佳[1] 陈北冬[1] 赵艳阳[1] 鲍利[1] 吴伟[1] 齐若梅[1]
机构地区:[1]北京医院/北京老年医学研究所卫计委老年医学重点实验室,北京100730
出 处:《中国药理学通报》2015年第11期1608-1614,共7页Chinese Pharmacological Bulletin
基 金:国家自然科学基金资助项目(No 81270379;81471051)
摘 要: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。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.
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