脓毒症心肌病患者外周血内皮细胞来源细胞外囊泡的表达及意义

Expression and significance of endothelial cell-derived extracellular vesicles in peripheral blood of patients with sepsis-induced cardiomyopathy

  • 摘要:
    目的 探讨脓毒症心肌病(SIC)患者外周血内皮细胞来源细胞外囊泡(EC-EVs)的表达特征及临床意义。
    方法 选取143例脓毒症患者作为研究对象,根据是否发生SIC将其分为心肌病组72例和非心肌病组71例。采集2组患者入院时外周血样本,分离并鉴定EC-EVs。比较2组患者外周血EC-EVs数量、凋亡情况以及EC-EVs中胱天蛋白酶-1(Caspase-1)的活性与表达水平。采用Spearman相关性分析法评估EC-EVs数量、Caspase-1活性与N末端脑钠肽前体(NT-proBNP)和心肌肌钙蛋白Ⅰ(cTnⅠ)的相关性; 采用多因素Logistic回归分析探讨脓毒症患者发生SIC的影响因素; 绘制受试者工作特征(ROC)曲线,分析EC-EVs数量、Caspase-1活性对SIC的预测价值。
    结果 2组样本中均成功分离出直径约为100 nm、具有完整膜结构并表达细胞外囊泡(EVs)标志分子(CD9、CD63、CD81)的EC-EVs。心肌病组外周血EC-EVs数量、EC-EVs凋亡水平、Caspase-1活性及蛋白表达水平均高于非心肌病组,差异有统计学意义(P < 0.05)。Spearman相关性分析结果显示, EC-EVs数量、Caspase-1活性分别与NT-proBNP(r=0.603、0.685, P < 0.001)、cTnI(r=0.474、0.711, P < 0.001)呈正相关。多因素Logistic回归分析结果显示, EC-EVs数量、Caspase-1活性、NT-proBNP水平、cTnI水平均为脓毒症患者发生SIC的独立影响因素(P < 0.05)。ROC曲线显示,外周血EC-EVs数量、Caspase-1活性预测SIC的曲线下面积分别为0.721、0.858。
    结论 SIC患者外周血EC-EVs数量及EC-EVs中Caspase-1活性显著增加,且EC-EVs数量、Caspase-1活性与脓毒症患者心功能及心肌损伤密切相关,有望成为预测SIC的生物标志物。

     

    Abstract:
    Objective To investigate the expression characteristics and clinical significance of endothelial cell-derived extracellular vesicles (EC-EVs) in the peripheral blood of patients with sepsis-induced cardiomyopathy (SIC).
    Methods A total of 143 sepsis patients were enrolled and divided into cardiomyopathy group (n=72) and non-cardiomyopathy group (n=71) based on occurrence of SIC. Peripheral blood samples were collected from patients in both groups upon admission for isolation and identification of EC-EVs. The number of EC-EVs, apoptosis, and the activity and expression levels of caspase-1 in EC-EVs were compared between the two groups. Spearman correlation analysis was used to assess the correlations of the number of EC-EVs, caspase-1 activity, and N-terminal pro-brain natriuretic peptide (NT-proBNP) with cardiac troponin Ⅰ (cTnⅠ). Multivariable Logistic regression analysis was conducted to explore the factors influencing the occurrence of SIC in sepsis patients. Receiver operating characteristic (ROC) curves were plotted to analyze the predictive value of the number of EC-EVs and caspase-1 activity for SIC.
    Results EC-EVs with a diameter of approximately 100 nm, intact membrane structure, and expression of extracellular vesicles (EVs) marker molecules (CD9, CD63, CD81) were successfully isolated from samples in both groups. The cardiomyopathy group had significantly higher numbers of EC-EVs in peripheral blood, EC-EV apoptosis levels, caspase-1 activity, and protein expression levels compared to the non-cardiomyopathy group(P < 0.05). Spearman correlation analysis revealed positive correlations between the number of EC-EVs and NT-proBNP (r=0.603, 0.685, P < 0.001), and between caspase-1 activity and cTnI (r=0.474, 0.711, P < 0.001). Multivariable Logistic regression analysis showed that the number of EC-EVs, caspase-1 activity, NT-proBNP levels, and cTnI levels were all independent influencing factors for the occurrence of SIC in sepsis patients (P < 0.05). The ROC curves indicated that the areas under the curve for predicting SIC based on the number of EC-EVs and caspase-1 activity in peripheral blood were 0.721 and 0.858, respectively.
    Conclusion The number of EC-EVs and caspase-1 activity in EC-EVs in the peripheral blood of SIC patients are significantly increased, and are closely related to cardiac function and myocardial injury in sepsis patients. Thus, they have the potential to become biomarkers for predicting SIC.

     

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