实用医学杂志2025，Vol.41Issue(3)：305-312,8.DOI:10.3969/j.issn.1006-5725.2025.03.001
四氢姜黄素通过下调ROS/p53信号通路抑制高糖诱导的血小板聚集和活化
Tetrahydrocurcumin attenuates high glucose-induced platelet aggregation and activation through down-regulating ROS/p53 signaling pathway
摘要
Abstract
Objective This study aims to explore the efficacy of tetrahydrocurcumin(THC),the major active metabolite of curcumin,on high glucose(HG)-induced human platelet aggregation and activation as well as to clarify the underlying mechanisms in vitro.Methods Purified platelets prepared from healthy subjects were pre-incubated with various concentrations of THC(0.5 µmol/L,1 µmol/L or 10 µmol/L)or vehicle control(0.05％DMSO)for 40 min at 37℃,followed by the stimulation of normal glucose(NG,5 mmol/L)or HG(25 mmol/L)for additional 90 min.The maximal aggregation rate was determined by an aggregometer.Flow cytometry was used to measure platelet surface expression of CD62P(a typical marker of platelet activation)and generation of total intraplatelet reactive oxygen species(ROS).Meanwhile,the phosphorylation level of platelet p53 was detected by Western blot assay.Results Compared with NG group,HG intervention significantly increased platelet aggrega-tion(P<0.05)and CD62P expression(P<0.001),which were greatly inhibited by different concentrations of THC(P<0.05).Mechanistically,when compared with solvent control,THC significantly decreased the level of total ROS production(P<0.001)and p53 phosphorylation(P<0.05).In addition,HG-induced total intraplatelet ROS generation(P<0.001)and p53 phosphorylation(P<0.05)were greatly attenuated by adding a ROS scavenger N-acetyl-L-cysteine(NAC).The combination of NAC with THC(10 µmol/L)showed no additive inhibitory effects(P>0.05).Moreover,platelet aggregation and activation induced by HG were greatly decreased by NAC and a p53 specific inhibitor PFT-µ(P<0.05).The combination of THC(10 µmol/L)and NAC resulted no additive inhibitory effects on HG-increased platelet aggregation and activation(P>0.05).THC(10 µmol/L)exhibited additive inhibitory effects on platelet aggregation(P<0.05)but no additive inhibitory effects on platelet activation when combined with PFT-µ(P>0.05).Conclusions THC exerts a protective effect on HG-induced platelet aggregation and activation possibly through down-regulating ROS/p53 signaling pathway in human platelets in vitro.The current study may provide potential value for THC to improve thrombosis in diabetes mellitus and the related chronic metabolic diseases.关键词
四氢姜黄素/血小板聚集/血小板活化/高糖/活性氧Key words
tetrahydrocurcumin/platelet aggregation/platelet activation/high glucose/reactive oxygen species分类
医药卫生引用本文复制引用
胡锦秋,毕晓艳,马军羽,李梦瑶,李荣,牙甫礼,张春梅..四氢姜黄素通过下调ROS/p53信号通路抑制高糖诱导的血小板聚集和活化[J].实用医学杂志,2025,41(3):305-312,8.基金项目
国家自然科学基金项目(编号:82260638) （编号:82260638）
云南省基础研究专项面上项目(编号:202401AT070081) （编号:202401AT070081）
