8-oxo-Guo通过血小板活化调控细胞因子分泌的研究  

Regulation of cytokine secretion by 8-oxo-Guo through platelet activation

作　　者：潘佳欣 李瑾[1] 蔡剑平[1] 奚桓[1] PAN Jiaxin;LI Jin;CAI Jianping;XI Huan(The Key Laboratory of Geriatrics,Beijing Institute of Geriatrics,Institute of Geriatric Medicine,Chinese Academy of Medical Sciences,Beijing Hospital/National Center of Gerontology of National Health Commission,P.R.China.Beijing100730,China)

机构地区：[1]北京医院,国家老年医学中心,国家卫生健康委北京老年医学研究所,国家卫生健康委老年医学重点实验室,中国医学科学院老年医学研究院,100730

出　　处：《中国老年保健医学》2025年第1期9-13,共5页Chinese Journal of Geriatric Care

基　　金：中央高校基本科研业务费专项资金资助(编号:BJ-2023-276);中央高水平医院临床科研业务费(编号:BJ-2023-246)。

摘　　要：目的探讨RNA氧化损伤的代谢产物8-oxo-Guo能否通过促进血小板活化,调控多种细胞因子的分泌。深入揭示氧化应激条件下血小板功能的变化,以及这种变化在炎症反应和免疫调控中的潜在作用,为理解氧化应激相关病理过程提供新的视角。方法本研究首先分离并纯化人血小板,然后使用8-oxo-Guo刺激血小板10分钟,以模拟氧化应激环境。然后,通过流式细胞术应用血小板膜表面活化标志物CD62P检测血小板活化状态,采用RayBio■QAH-CAA-2000试剂盒定量检测8-oxo-Guo刺激人血小板后120种细胞因子的水平变化。采用GraphPad Prism 9.0.0进行数据分析,使用Student's t检验分析两组间差异。结果与对照组相比,8-oxo-Guo显著促进了血小板活化,其特征为CD62P表达水平的显著升高。同时,8-oxo-Guo处理后的血小板分泌的多种细胞因子也发生显著变化,其中炎症趋化因子MCP-3、MIP-3α、MIP-3β和MDC的表达显著上调,生长因子EG-VEGF、FGF-4、NT-3和BMP-7的表达显著下调。GO富集分析显示变化的细胞因子主要集中在免疫调节、炎症反应和细胞迁移等方面。这些结果提示8-oxo-Guo在调控血小板功能及相关细胞因子释放方面具有重要作用。结论8-oxo-Guo可以通过促进血小板的活化影响多种细胞因子水平的变化,这一发现不仅揭示了氧化应激条件下血小板功能调控的新机制,也为开发针对氧化应激相关疾病的新型治疗策略提供了理论基础和实验依据。Objective The objective of this study was to evaluate whether 8-oxo-Guo,an oxidative RNA damage metabolite,influences cytokine secretion by enhancing platelet activation.This research aims to shed light on alterations in platelet function under oxidative stress and their potential implications for inflammatory responses and immune regulation.By exploring these mechanisms,the study provides new perspectives on the pathological processes associated with oxidative stress.Methods Human platelets were first isolated and purified,followed by stimulation with 8-oxo-Guo for 10 minutes to simulate an oxidative stress environment.Platelet activation was assessed using flow cytometry to measure the surface expression of the activation marker CD62P.Additionally,changes in the levels of 120 cytokines after 8-oxo-Guo stimulation were quantified using the RayBio■QAH-CAA-2000 kit.Data analysis was performed using GraphPad Prism 9.0.0,and group differences were evaluated with Student's t-test,considering P<0.05 as statistically significant.Results Compared with the control group,8-oxo-Guo markedly enhanced platelet activation,as evidenced by a significant increase in CD62P expression levels.Furthermore,the secretion profiles of multiple cytokines from platelets treated with 8-oxo-Guo exhibited significant alterations.The expression levels of inflammatory chemokines,including MCP-3,MIP-3α,MIP-3β,and MDC,were significantly upregulated,while the levels of growth factors,such as EG-VEGF,FGF-4,NT-3,and BMP-7,were markedly downregulated.GO enrichment analysis indicated that the altered cytokines were primarily associated with immune regulation,inflammatory responses,and cell migration.These findings highlight the critical role of 8-oxo-Guo in modulating platelet function and cytokine release.Conclusion This study demonstrates that 8-oxo-Guo influences cytokine level changes by promoting platelet activation unveils a novel mechanism underlying platelet function regulation under oxidative stress.Furthermore,it provides a theoretical

关 键 词：RNA氧化损伤 8-氧化鸟苷 血小板活化 细胞因子 

分 类 号：R363[医药卫生—病理学]