急性冠脉综合征发生与外周血红细胞源微粒致血栓活性的关系研究

Association Study between Onset of Acute Coronary Syndrome and Thrombogenic Activity Induced by Peripherial Red Blood Cell-derived Microparticles

目的 通过评估红细胞源微粒（RMPs）和急性冠脉综合征（ACS）发病之间的关联,描述RMPs在急性冠状动脉血栓形成过程中发挥的作用.方法 研究对象分ACS组（n=200）,其分为急性心肌梗死（AMI,n=100）和不稳定型心绞痛组（UAP,n=100）,对照组为非冠心病组（n=100）.获得患者知情同意后,收集ACS组以及对照组的外周血,离心后加入钙离子载体A23187,得到MPs.用特异性红细胞微粒抗体（glycophorine A）标记RMPs,后经流式细胞仪定量分析.在体外,将ACS患者血浆中提取的RMPs加入对照组血浆中,在荧光标记的血栓底物作用下诱导血栓形成并用荧光光度仪检测RMPs的致血栓活性.结果 RMPs水平在ACS的AMI亚组（163×102）和UAP亚组（96×102）都明显高于对照组（12×102,P＜0.05）.ACS患者在每一个时间段相对荧光单位较对照组显著提高（P＜0.05）.研究结果显示,高浓度的MPs更易导致血栓形成且所需时间较短,差异有统计学意义（P＜0.05）.结论 ACS组的外周血中RMPs水平明显升高,提示RMPs参与了ACS的发生、发展过程.MPs诱导的血栓形成峰值前移,提示RMPs可能诱导凝血酶形成,揭示ACS发生急性血栓与RMPs有关.

Objective By evaluating the association between red blood cell-derived microparticles（RMPs） and the onset of ACS,this study ultimately aimed to reveal the pathological mechanism of ACS,understand the progress of the disease,and characterize the role of RMPs in acute thrombosis in the coronary artery of ACS patients.Methods Inclusion criteria：enrolled participants were ACS patients and non-coronary artery disease （non-CAD） subjects who were diagnosed at the outpatient department of cardiology in the People＇s Hospital of Xinjiang Uygur Autonomous Region.After informed consent was obtained from subjects,peripheral blood was collected from ACS patients and non-CAD subjects.The RMPs were then separated by Ca2＋ vector A23187 after precipitating the RBCs by centrifugation.The RMPs from ACS patients and non-CAD subjects were labeled with a RBC specific antibody,glycophorine A,and subjected to flow cytometry for quantification.In vitro,RMPs from the ACS patients were added into the plasma from non-CAD subjects to induce thrombosis with the fluorescent thgrombin substrates,and the thrombogenic activity of RMPs was examined by fluorescence spectrometer.Results The level of RMPs in the AMI subgroup（163 × 102） and the UAP subgroup（96 × 102） of ACS group were both significantly higher than the level of RMPs in non-CAD group（12 × 102,P ＜ 0.05）.The relative fluorescence unit of ACS patients was significantly greater than that of non-CAD subject at every time point（P ＜ 0.05）.The results indicated that a higher concentration of MPs resulted in a stronger thrombogenic activity and shorter thrombosis time.Conclusion The level of RMPs in the peripheral blood of ACS patients was significantly higher,indicated the active RBC-derived MPs（RMPs） are increase in patients with acute coronary syndrome（ACS）,and these RMPs may play an important role during the development of ACS.The peak of the RMPs-induced thrombosis was shifted forward,which may induce the formation of thrombin.