[Association between CD137 and ischemia-reperfusion injury in patients with acute ST-segment elevation myocardial infarction].

Objective: To explore the relationship between the levels of serum soluble CD137 (sCD137) and membrane-bound CD137 (mCD137) and the occurrence of ischemia reperfusion injury (IRI) in patients with acute ST-segment elevation myocardial infarction (STEMI). Methods: This is a cross-sectional study. Consecutive patients with acute STEMI, who underwent emergency percutaneous coronary intervention (PCI) in the Department of Cardiology, Jiangsu University Affiliated Hospital from May 2019 to September 2020, were enrolled. According to the absence or presence of IRI, patients were divided into IRI group and non-IRI group. Clinical data of the two groups were collected and compared. sCD137 level was detected by enzyme linked immunosorbent assay. Ficoll density gradient centrifugation was used to separate peripheral blood mononuclear cells (PBMC) and RNA was extracted, mCD137 mRNA expression level was detected by PCR. Serum sCD137 levels and the mCD137 mRNA levels of PBMC before, after PCI and 24 hours after PCI were compared. The correlation between serum sCD137 level, PBMC mCD137 mRNA level and clinical indicators was observed. The univariate and multivariate logistic binary regression analyses were performed to evaluate the related risk factors of IRI. ROC curve was used to analyze the predictive value of defined parameters for IRI. Results: A total of 112 STEMI patients were enrolled. There were 42 cases (of which 33 were males (78.6%), mean age was (58.6±12.7) years) in non-IRI group and 70 cases(of which 56 were males (80.0%), mean age was (64.5±11.6) years) in IRI group. Compared with the non-IRI group, patients in the IRI group had longer hospital stays, older age, lower rates of obesity, lower systolic and diastolic blood pressure at admission, higher proportion of the the right coronary artery as culprit vessel, lower rate of the use of angiotensin-converting enzyme inhibitor/angiotensin-Ⅱ receptor blocker/angiotensin receptor neprilysin inhibitor, higher levels of urea nitrogen and creatinine, lower glomerular filtration rate, lower triglycerides, higher D-dimer and B-type natriuretic peptidemax, higher proportion of Killip grade Ⅳ and cardiovascular adverse events (all P<0.05). sCD137 levels at the preoperative, postoperative and 24 hours after surgery were significantly higher in the IRI group than in the non-IRI group, while the mRNA levels of CD137 was similar between the two groups. The level of sCD137 in patients after PCI was lower than that before operation, the level of mCD137 mRNA was higher than that before operation (P<0.05). Serum sCD137 levels were positively correlated with hospitalization days, age, B-type natriuretic peptide, creatinine, ischemic time, C Reactive protein (CRP) and CRP/albumin (P<0.05), and negatively correlated with body mass index, glomerular filtration rate and albumin (P<0.05). The mCD137 mRNA expression level of PBMC was positively correlated with hospital stay, age, B-type natriuretic peptide, ischemic time, CRP and CRP/albumin (P<0.05), and negatively correlated with body mass index, glomerular filtration rate, albumin (P<0.05). Multivariate logistic regression analysis showed that higher sCD137 (OR=1.038, 95%CI: 1.009-1.069), aspartate aminotransferase, (OR=1.029, 95%CI: 1.009-1.050) and lower albumin (OR=0.829, 95%CI: 0.703-0.829) before surgery were independent risk factors of IRI (P<0.05). Receiver operating characteristic curve showed that the area under the curve of sCD137 was 0.672 (95%CI: 0.574-0.770, P=0.002) for the prediction of IRI, the best cut-off value was 28.43×10-3 μg/L with sensitivity of 95.2% and specificity of 48.6%. Conclusion: The significantly increased level of sCD137 in acute STEMI patients is positively correlated with reperfusion injury, which is an independent risk factor of IRI and may be related to the prognosis of patients with IRI.目的： 探讨急性ST段抬高型心肌梗死（STEMI）患者血清可溶型CD137（sCD137）和膜结合型CD137（mCD137）水平与缺血再灌注损伤（IRI）的关系。 方法： 本研究为横断面研究。连续纳入2019年5月至2020年9月于江苏大学附属医院心内科接受急诊经皮冠状动脉介入治疗（PCI）的急性STEMI患者，依据是否发生IRI分为IRI组和非IRI组。收集并比较两组患者的临床资料，采用酶联免疫吸附法检测两组患者血清sCD137水平，采用Ficoll密度梯度离心法分离外周血单个核细胞（PBMC）并提取RNA，聚合酶链式反应法检测mCD137 mRNA表达水平。分析PCI术前、术后即刻、术后24 h血清sCD137及PBMC的mCD137 mRNA变化趋势。采用Spearman相关分析术前血清sCD137、术后即刻PBMC的mCD137 mRNA水平与临床指标的相关性。采用单因素和多因素logistic回归分析影响IRI的独立相关因素并采用受试者工作特征（ROC）曲线分析其预测价值。 结果： 最终纳入112例STEMI患者，非IRI组42例，男性33例（78.6%），年龄（58.6±12.7）岁；IRI组70例，男性56例（80.0%），年龄（64.5±11.6）岁。与非IRI组相比，IRI组的患者住院天数长，年龄大，肥胖比例低，入院时收缩压、舒张压低，罪犯血管为右冠状动脉的比例高，血管紧张素转化酶抑制剂/血管紧张素Ⅱ受体阻滞剂/血管紧张素受体脑啡肽酶抑制剂的使用率低，尿素氮、肌酐高，肾小球滤过率低，甘油三酯低，D-二聚体和B型钠尿肽max高，Killip分级Ⅳ级的比例和心血管不良事件发生率高（P均<0.05）。IRI组术前、术后即刻、术后24 h的sCD137水平均高于非IRI组；两组mCD137 mRNA水平无差异。两组患者PCI术后即刻sCD137水平均较术前降低，mCD137 mRNA水平较术前升高（P<0.05）。相关性分析显示，急性STEMI患者血清sCD137水平与住院天数、年龄、B型钠尿肽、肌酐、缺血时间、C反应蛋白（CRP）、CRP/血清白蛋白（Alb）呈正相关（P<0.05），与体重指数、肾小球滤过率、Alb呈负相关（P<0.05）。PBMC的mCD137 mRNA表达水平与住院天数、年龄、B型钠尿肽、缺血时间、CRP、CRP/Alb呈正相关（P<0.05），与体重指数、肾小球滤过率、Alb呈负相关（P<0.05）。多因素logistic回归分析显示，术前sCD137（OR=1.038，95%CI 1.009~1.069）升高、天冬氨酸氨基转移酶（OR=1.029，95%CI 1.009~1.050）升高、Alb（OR=0.829，95%CI 0.703~0.829）下降是IRI发生的独立正相关因素（P均<0.05）。其中sCD137预测IRI的曲线下面积（AUC）=0.672，95%CI 0.574~0.770（P=0.002），最佳阈值为28.43×10-3 μg/L，敏感度为95.2%，特异度为48.6%。 结论： 发生再灌注损伤的急性STEMI患者sCD137水平显著升高，是IRI发生的独立正相关因素，可能与IRI的预后相关。.