上海交通大学学报（医学版）2025，Vol.45Issue(12)：1568-1577,10.DOI:10.3969/j.issn.1674-8115.2025.12.002
黄嘌呤氧化酶在高尿酸血症患者血小板高反应性中的作用及机制
Role and mechanism of xanthine oxidase in platelet hyperreactivity of hyperuricemia patients
摘要
Abstract
Objective·To analyze the correlation between platelet activation indices and xanthine oxidase(XO)activity in patients and the underlying molecular mechanisms.Methods·Between January 2023 and June 2025,24 patients with hyperuricemia were recruited from the Department of Rheumatology and the Physical Examination Center of Huashan Hospital,Fudan University.Twenty-four healthy volunteers from the same center during the same period served as the healthy control group.Demographic data(age,gender),comorbidities,and medication history of all subjects were collected,and their fasting venous blood was drawn.Washed platelets were prepared for subsequent assays.The expression levels of P-selectin and platelet activation complex-1(PAC-1)on the platelet surface were determined by flow cytometry,while platelet XO activity was measured via an absorbance assay.Spearman correlation analysis was performed to evaluate the relationships between uric acid levels,XO activity,and platelet activation markers.The effects of various concentrations of febuxostat on platelet aggregation induced by collagen,adenosine diphosphate(ADP),U46619,and thrombin were assessed.Platelet spreading on fibrinogen was analyzed.Furthermore,thrombin-induced intraplatelet reactive oxygen species(ROS)production was measured.Results·Compared with the healthy control group,patients in the hyperuricemia group exhibited significantly higher platelet surface expression of P-selectin and PAC-1(both P<0.05).However,neither marker showed a significant correlation with serum uric acid levels(both P>0.05).Platelet XO activity showed a positive correlation with thrombin-induced P-selectin expression(r=0.453,P=0.001)and PAC-1 expression(r=0.478,P=0.001).Febuxostat at concentrations of 50 μmol/L and 100 μmol/L significantly inhibited collagen,ADP,U46619,and thrombin-induced platelet aggregation and also significantly suppressed the spreading of platelets on fibrinogen.These inhibitory effects were statistically significant(all P<0.05)and intensified with increasing concentrations of febuxostat,demonstrating a concentration-dependent manner.Meanwhile,febuxostat treatment significantly reduced intraplatelet ROS generation in response to thrombin stimulation(P<0.05).Conclusion·Platelet activation markers are higher in hyperuricemia patients than in the healthy control group.The expression levels of P-selectin and PAC-1 on the platelet surface show a positive correlation with intraplatelet XO activity.XO inhibitors can modulate platelet activation by reducing intracellular ROS production.关键词
黄嘌呤氧化酶/血小板/活性氧/高尿酸血症Key words
xanthine oxidase/platelet/reactive oxygen species/hyperuricemia分类
医药卫生引用本文复制引用
高稳,潘杰松,赵奕凯,罗心平,李剑..黄嘌呤氧化酶在高尿酸血症患者血小板高反应性中的作用及机制[J].上海交通大学学报（医学版）,2025,45(12):1568-1577,10.基金项目
国家自然科学基金(82470345) （82470345）
复旦大学附属华山医院院级科研基金(2018QD122). National Natural Science Foundation of China(82470345) （2018QD122）
Scientific Fund of Huashan Hospital,Fudan University(2018QD122). （2018QD122）
