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循环细胞外囊泡粒径特征与体外循环心脏手术后凝血功能的关系
曹洪宇
袁浩翔
陈超
简宇鹏
李钰泉
刘晓军
马振升
李艳
区景松
作者及单位信息
·
DOI： 10.3760/cma.j.cn112434-20241231-00337
The relationship between size distribution of circulating extracellular vesicles and coagulation function after cardiac surgery
Cao Hongyu
Yuan Haoxiang
Chen Chao
Jian Yupeng
Li Yuquan
Liu Xiaojun
Ma Zhensheng
Li Yan
Ou Jingsong
Authors Info & Affiliations
Cao Hongyu
Department of Cardiac Surgery, Cardiovascular Diseases Institute, the First Affiliated Hospital, Sun Yat-sen University, National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou 510080, China
Yuan Haoxiang
Department of Cardiac Surgery, Cardiovascular Diseases Institute, the First Affiliated Hospital, Sun Yat-sen University, National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou 510080, China
Chen Chao
Department of Cardiac Surgery, Cardiovascular Diseases Institute, the First Affiliated Hospital, Sun Yat-sen University, National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou 510080, China
Jian Yupeng
Department of Cardiac Surgery, Cardiovascular Diseases Institute, the First Affiliated Hospital, Sun Yat-sen University, National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou 510080, China
Li Yuquan
Department of Cardiac Surgery, Cardiovascular Diseases Institute, the First Affiliated Hospital, Sun Yat-sen University, National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou 510080, China
Liu Xiaojun
Department of Cardiac Surgery, Cardiovascular Diseases Institute, the First Affiliated Hospital, Sun Yat-sen University, National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou 510080, China
Ma Zhensheng
Department of Cardiac Surgery, Cardiovascular Diseases Institute, the First Affiliated Hospital, Sun Yat-sen University, National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou 510080, China
Li Yan
Department of Cardiac Surgery, Cardiovascular Diseases Institute, the First Affiliated Hospital, Sun Yat-sen University, National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou 510080, China
Ou Jingsong
Department of Cardiac Surgery, Cardiovascular Diseases Institute, the First Affiliated Hospital, Sun Yat-sen University, National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Diseases, NHC Key Laboratory of Assisted Circulation and Vascular Diseases (Sun Yat-sen University), Key Laboratory of Assisted Circulation and Vascular Diseases, Chinese Academy of Medical Sciences, Guangdong Provincial Engineering and Technology Center for Diagnosis and Treatment of Vascular Diseases, Guangdong Provincial Key Laboratory of Brain Function and Disease, Guangzhou 510080, China
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DOI： 10.3760/cma.j.cn112434-20241231-00337
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摘要

目的探讨体外循环(CPB)心脏手术前后循环细胞外囊泡(EVs)粒径的变化与术后凝血功能之间的关系。

方法共纳入103例接受CPB心内直视手术的患者，分别在术前、术后12 h和术后3天采集静脉血标本。同时，选取50例年龄、性别匹配的健康志愿者作为对照组。采用梯度离心法分离EVs，并利用动态光散射(DLS)方法检测EVs的粒径分布。通过分析EVs的粒径特征(包括峰直径、峰高和四分位数间距 IQR)，探讨其与CPB术后凝血功能的相关性。

结果与术后凝血功能正常的患者相比，术后出现凝血功能障碍的患者EVs的峰直径和 IQR较低，峰高显著升高。 Logistic回归分析表明，术后EVs升高的峰高以及较低的峰直径和 IQR是发生凝血功能障碍的危险因素。术后12 h EVs峰高诊断凝血功能障碍的曲线下面积( AUC)0.76，在最佳截值8.2时的阳性预测值85%；术后12 h IQR的 AUC 0.84，在最佳截值125.05 nm时的敏感度83%，特异性82%，阴性预测值86%。

结论循环EVs的粒径特征与CPB心脏手术后凝血功能有一定的相关性，可作为辅助预测手术后凝血功能障碍的新标志物。

细胞外囊泡;心脏手术;凝血功能;体外循环
ABSTRACT

ObjectiveTo investigate the relationship between the changes in extracellular vesicles (EVs) size distribution before and after cardiopulmonary bypass (CPB) cardiac surgery and postoperative coagulation function.

MethodsA total of 103 patients undergoing cardiac surgery with CPB were enrolled. Venous blood samples were collected at preoperation, postoperative 12 h and 3 days. Additionally, 50 age- and gender-matched healthy volunteers served as a control group. EVs were isolated using gradient centrifugation, and their size distribution was assessed by dynamic light scattering (DLS). The relationship between EV size characteristics, including peak diameter, peak height, and interquartile range( IQR), and postoperative coagulation function was analyzed.

ResultsCompared to patients with normal postoperative coagulation function, those with postoperative coagulation dysfunction had lower size at peak and IQR, and significantly higher peak intensity. Logistic regression analysis indicated that elevated peak intensity and lower size at peak and IQR were risk factors for coagulation dysfunction. The area under the curve ( AUC) for diagnosing coagulation dysfunction with 12 h postoperative EVs peak intensity was 0.76, with a positive predictive value of 85% at the optimal cutoff of 8.2; the AUC for IQR was 0.84, with a sensitivity of 83%, specificity of 82%, and negative predictive value of 86% at the optimal cutoff of 125.05 nm.

ConclusionThe size distribution of circulating EVs show a correlation with coagulation function after cardiac surgery with CPB and may serve as a novel biomarker to predict postoperative coagulation dysfunction.

Extracellular vesicles;Cardiac surgery;Coagulation;Cardiopulmonary bypass
Ou Jingsong Email: nc.defudabe.usys.liamsjuo
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引用本文

曹洪宇,袁浩翔,陈超,等. 循环细胞外囊泡粒径特征与体外循环心脏手术后凝血功能的关系[J]. 中华胸心血管外科杂志,2025,41(03)：183-190.

DOI:10.3760/cma.j.cn112434-20241231-00337

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体外循环(cardiopulmonary bypass，CPB)作为一种在心脏手术中替代心脏和肺功能的关键技术已广泛应用于各类心脏手术中 [ 1 , 2 ]。然而，凝血功能障碍作为CPB术后常见的并发症，其发生与多种因素有关，包括消耗性凝血病、血小板损伤、低温暴露以及血液稀释等 [ 3 , 4 , 5 , 6 ]。循环细胞外囊泡(extracellular vesicles，EVs)是细胞在受到刺激或凋亡时分泌的一类直径100～1 000 nm的膜囊泡，它们在细胞间信息传递、血管调节、炎症反应、细胞增殖与凋亡等生命过程中扮演着重要角色 [ 7 , 8 , 9 ]。我们前期研究发现EVs可以预测CPB心脏手术后心功能不全、急性肺损伤和急性肾损伤等多个器官的并发症 [ 8 , 9 , 10 , 11 , 12 ]。过往研究表明，在心脏手术患者中，术后EVs的含量尤其是来自于血小板的EVs含量明显升高 [ 13 , 14 ]，并且来源于血小板或平滑肌细胞的EVs有促进血栓形成的功能 [ 13 , 14 , 15 ]，可能与术后凝血功能障碍的发生有关。我们前期研究发现，尽管CPB心脏手术后发生急性肺损伤患者EVs数量未发生改变，但EVs的粒径分布发生变化，可用于预测急性肺损伤 [ 10 ]。但是否可以通过EVs粒径特征预测CPB心脏手术后凝血功能变化尚未清楚。本研究旨在探讨CPB术后EVs的粒径变化与术后凝血功能异常之间的关系，为临床预测CPB术后凝血功能异常提供新的标志物。
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曹洪宇：数据分析、论文写作；袁浩翔、陈超：实验检测；简宇鹏、李钰泉、刘晓军、马振升、李艳：标本收集、数据整理；区景松：研究指导、论文审阅、经费支持

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国家重点研发计划项目 (2021YFA0805100)
国家自然科学基金重大项目课题和重大研究计划重点项目 (82495171、92268202)
中国医学科学院中央级公益性科研院所基本科研业务费专项资金 (2023-PT320-03)
广东省自然科学基金青年提升项目 (2024A1515030041)
中山大学临床医学研究5010计划项目 (2014002)
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