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临床上心房纤维颤动(房颤)是最常见的持续性心律不齐之一,其死亡率及发生率都较高[1]。研究[2]发现房颤最终会导致脑梗死、心肌梗死、心力衰竭等心脑血管终端事件。相关流行病调查研究[3]发现,房颤的发病率逐年上升。但就目前治疗方案来说,仍具有较多的局限性:房颤射频消融术潜在并发症以及复发率较高;抗心律失常药物疗效有限且不良反应强[4]。因此房颤潜在的病理机制成为我们研究的重点,早期研究[5]证实房颤发生的基础病因主要与心脏结构重构相关,而心脏结构重构的根本原因是心肌纤维化。心肌细胞的炎症反应、钙超载、氧化应激以及心脏成纤维细胞的活化等因素与心肌纤维化有关[6-8]。早期研究证实白细胞介素-1β(IL-1β)作为炎症因子家族成员之一,可参与大量的炎症以及应激反应[9],而钙超载可诱导钙蛋白酶-2(Calpain-2)的激活,并参与多种钙调通路[10]。因此,本研究主要通过分析房颤病人血清中IL-1β、Calpain-2水平和超声心动图左心房内径(LAD)、左心室舒张期内径(LVDd)、左心室射血分数(LVEF)和左心室缩短分数(FS)指标,探究房颤发生与发展的相关病理机制,为临床治疗开辟新思路。
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选取2019年1月至2020年11月在蚌埠医学院第一附属医院住院房颤病人150例为观察组,依照《2020年心房颤动的诊断和管理指南》将其分为阵发性房颤病人84例和非阵发性房颤病人66例。对照组选用同时段体检健康者120名。入组标准:参考欧洲心脏病协会(ESC)联合欧洲心胸外科协会(EACTS)颁发的《2020年心房颤动的诊断和管理指南》的诊疗标准确诊房颤病人;性别不限;年龄≥18岁;同时检查IL-1β、Calpain-2水平以及超声心动图。排除标准:慢性阻塞性肺疾病、风湿性心脏病、心脏瓣膜病、先天性心脏病、肝肾功能不全、良恶性肿瘤、脑血管意外等。2组的性别、高血压、糖尿病、肝肾功能等基础信息差异均无统计学意义(P>0.05)(见表 1)。
分组 n 年龄/岁 男 高血压 糖尿病 白细胞/(×109/L) 血小板/(×109/L) 肌酐/(mmol/L) 天冬氨酸氨基转移酶(U/L) 丙氨酸氨基转移酶/(U/L) 低密度脂蛋白/(mmol/L) 观察组 150 65(55,73) 87 73 16 5.31(4.71,6.68) 195.00(174.75,228.25) 60.00(51.00,67.00) 20.00(16.75,26.00) 17.00(13.00,24.00) 1.94(1.49,2.38) 对照组 120 46(43,51) 70 55 11 5.44(4.79,6.42) 207.00(177.25,239.75) 59.00(56.00,64.00) 19.00(17.00,22.75) 15.00(12.25,23.75) 1.78(1.48,2.08) zc — 10.14 0.00* 0.22* 0.17* 0.11 1.51 0.00 0.78 1.20 1.66 P — < 0.01 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 *示χ2值 表 1 2组基线资料比较[M(P25,P75)]
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留取2组外周静脉血5 mL,离心后提取上层血清,将血清保存至-80 ℃冰箱。所有标本中IL-1β、Calpain-2水平统一采用酶联免疫吸附法(ELISA)检测。白细胞、血小板、肌酐、丙氨酸氨基转移酶、天冬氨酸氨基转移酶、低密度脂蛋白等血清学指标由我院检验科测得。利用超声心动图检测房颤病人住院房颤发作期间以及健康体检者的LAD、LVDd、LVEF、FS。
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采用两独立样本非参数检验(Z检验)、χ2检验、多个独立样本非参数(H)检验、Pearson相关性分析和二元logistic回归分析。
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与对照组相比,阵发性房颤组和非阵发性房颤组IL-1β、Calpain-2、LAD、LVDd水平均升高,LVEF、FS水平下降;同时与阵发性房颤组相比,非阵发性房颤组中IL-1β、Calpain-2、LAD、LVDd水平上升,且LVEF、FS水平下降,差异均有统计学意义(P < 0.05~P < 0.01)(见表 2)。
分组 IL-1β/(pg/mL) Calpain-2/(U/L) LAD/mm LVDd/mm LVEF/% FS/% 对照组 13.42(8.96,18.86) 285.00(195.19,354.81) 31.00(28.25,34.75) 46.00(44.00,48.00) 57.00(54.00,61.00) 31.00(29.00,35.00) 阵发性房颤 20.49(16.21,25.30)* 395.00(331.15,447.31)* 34.00(32.00,40.00)* 49.00(46.00,50.00)* 55.00(52.00,58.00)* 30.00(27.00,32.00)* 非阵发性房颤 22.43(19.06,28.19)*△ 426.54(373.85,635.19)*△ 44.50(38.50,51.00)*△ 55.00(47.75,61.00)*△ 49.00(40.75,55.00)*△ 25.50(21.00,28.00)*△ Hc 92.96 95.23 74.55 45.99 47.67 64.53 P < 0.05 < 0.01 < 0.01 < 0.01 < 0.05 < 0.01 H检验:与正常对照组比较*P < 0.05;与阵发性房颤组比较△P < 0.05 表 2 IL-1β、Calpain-2及心脏彩超结果结果比较[M(P25,P75)]
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二元logistic回归提示:年龄大、IL-1β、Caplain-2、LAD水平升高是房颤发生的危险因素(P < 0.01)(见表 3)。
变量 B SE Waldχ2 P OR(95%CI) 年龄 0.161 0.025 43.60 < 0.01 1.183(1.124~1.243) IL-1β 0.182 0.039 21.38 < 0.01 1.201(1.113~1.287) Caplain-2 0.010 0.002 11.75 < 0.01 1.014(1.004~1.009) LAD 0.092 0.031 8.60 < 0.01 1.093(1.028~1.162) 表 3 房颤影响二元logistic回归结果
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在Spearman相关性检验结果中,IL-1β与LAD、LVDd呈正相关关系(P < 0.01),与LVEF、FS呈负相关关系(P < 0.01);同样Caplain-2与LAD、LVDd呈正相关关系(P < 0.01),与LVEF、FS呈负相关关系(P < 0.01)(见表 4)。
指标 IL-1β Caplain-2 r P r P LAD 0.321 < 0.01 0.358 < 0.01 LVDd 0.283 < 0.01 0.342 < 0.01 LVEF -0.288 < 0.01 -0.288 < 0.01 FS -0.334 < 0.01 -0.378 < 0.01 表 4 IL-1β、Caplain-2与心脏彩超结果的相关性分析
心房颤动病人IL-1β、Calpain-2水平与心脏结构重构的相关性研究
Relationship between IL-1β, Calpain-2 levels and cardiac structure in patients with atrial fibrillation
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摘要:
目的探讨心房颤动(房颤)病人血清中白细胞介素-1β(IL-1β)、钙蛋白酶-2(Calpain-2)表达水平及与心脏结构重构的相关性。 方法选取确诊为房颤的病人150例为观察组, 依据2020年ESC/EACTS房颤诊断和管理指南将其分为非阵发性房颤组和阵发性房颤组; 选取同时段健康体检者120名作为对照组。分别检测血清IL-1β、Calpain-2以及超声心动图中左心室舒张期内径(LVDd)、左心房内径(LAD)、左心室射血分数(LVEF)和左心室缩短分数(FS)等指标, 比较3组不同指标是否存在差异; 运用Pearson相关性分析血清IL-1β、Calpain-2与超声心动图检查结果的相关性; 采用二元logistic回归分析, 探寻房颤的危险因素。 结果观察组中IL-1β、Calpain-2含量显著高于对照组(P < 0.05), 而且非阵发性房颤病人明显高于阵发性房颤病人(P < 0.05)。在超声心动图指标中非阵发性房颤组LAD、LVDd均高于阵发性房颤组以及对照组(P < 0.05), LVEF、FS均低于阵发性房颤组及对照组(P < 0.05)。二元logistic回归分析显示IL-1β、Calpain-2是房颤发生的危险因素。Spearman相关性分析显示IL-1β、Calpain-2与LAD、LVDd呈正相关关系(P < 0.01), 而与LVEF、FS呈显著负相关关系(P < 0.01)。 结论IL-1β、Calpain-2与LAD、LVDd呈正相关关系, 参与了心脏结构重构过程, 进而促进了房颤的发生与发展。 Abstract:ObjectiveTo investigate the relationship between the expression levels of interleukin-1β(IL-1β), calpain-2(Calpain-2) and cardiac remodeling in patients with atrial fibrillation. MethodsA total of 150 patients diagnosed with atrial fibrillation(AF) were selected as the observation group, and divided into non-paroxysmal AF group and paroxysmal AF group according to the 2020 ESC/EACTS GUIDELINES for the diagnosis and Management of AF.A total of 120 healthy subjects at the same period were selected as the control group.Serum IL-1β, Calpain-2 contents, left ventricular diastolic diameter(LVDd), left atrial diameter(LAD), left ventricular ejection fraction(LVEF) and left ventricular shortening fraction(FS) were detected by echocardiography, and the differences among the three groups were compared.Pearson correlation was used to analyze the correlation between serum IL-1β and Calpain-2 contents and the results of echocardiography.Binary logistic regression was used to explore the risk factors of AF. ResultsThe contents of serum IL-1β and Calpain-2 in the observation group were significantly higher than those in the control group(P < 0.05), and those in the patients without paroxysmal AF were significantly higher than those in the patients with paroxysmal AF(P < 0.05).The indexes of LAD and LVDd in non-paroxysmal AF group were higher than those in paroxysmal AF group and control group(P < 0.05), but LVEF and FS were lower than those in paroxysmal AF group and control group(P < 0.05).Spearman correlation analysis showed that IL-1β and Calpain-2 were positively correlated with LAD and LVDd(P < 0.01), but negatively correlated with LVEF and FS(P < 0.01).Binary logistic regression analysis showed that IL-1β and Calpain-2 were the risk factors for AF. ConclusionsIL-1β and Calpain-2 were positively correlated with LAD and LVDd, and were involved in the process of cardiac remodeling, thus promoting the occurrence and development of atrial fibrillation. -
Key words:
- atrial fibrillation /
- interleukin-1β /
- calpain-2 /
- cardiac structural remodeling
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表 1 2组基线资料比较[M(P25,P75)]
分组 n 年龄/岁 男 高血压 糖尿病 白细胞/(×109/L) 血小板/(×109/L) 肌酐/(mmol/L) 天冬氨酸氨基转移酶(U/L) 丙氨酸氨基转移酶/(U/L) 低密度脂蛋白/(mmol/L) 观察组 150 65(55,73) 87 73 16 5.31(4.71,6.68) 195.00(174.75,228.25) 60.00(51.00,67.00) 20.00(16.75,26.00) 17.00(13.00,24.00) 1.94(1.49,2.38) 对照组 120 46(43,51) 70 55 11 5.44(4.79,6.42) 207.00(177.25,239.75) 59.00(56.00,64.00) 19.00(17.00,22.75) 15.00(12.25,23.75) 1.78(1.48,2.08) zc — 10.14 0.00* 0.22* 0.17* 0.11 1.51 0.00 0.78 1.20 1.66 P — < 0.01 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 *示χ2值 表 2 IL-1β、Calpain-2及心脏彩超结果结果比较[M(P25,P75)]
分组 IL-1β/(pg/mL) Calpain-2/(U/L) LAD/mm LVDd/mm LVEF/% FS/% 对照组 13.42(8.96,18.86) 285.00(195.19,354.81) 31.00(28.25,34.75) 46.00(44.00,48.00) 57.00(54.00,61.00) 31.00(29.00,35.00) 阵发性房颤 20.49(16.21,25.30)* 395.00(331.15,447.31)* 34.00(32.00,40.00)* 49.00(46.00,50.00)* 55.00(52.00,58.00)* 30.00(27.00,32.00)* 非阵发性房颤 22.43(19.06,28.19)*△ 426.54(373.85,635.19)*△ 44.50(38.50,51.00)*△ 55.00(47.75,61.00)*△ 49.00(40.75,55.00)*△ 25.50(21.00,28.00)*△ Hc 92.96 95.23 74.55 45.99 47.67 64.53 P < 0.05 < 0.01 < 0.01 < 0.01 < 0.05 < 0.01 H检验:与正常对照组比较*P < 0.05;与阵发性房颤组比较△P < 0.05 表 3 房颤影响二元logistic回归结果
变量 B SE Waldχ2 P OR(95%CI) 年龄 0.161 0.025 43.60 < 0.01 1.183(1.124~1.243) IL-1β 0.182 0.039 21.38 < 0.01 1.201(1.113~1.287) Caplain-2 0.010 0.002 11.75 < 0.01 1.014(1.004~1.009) LAD 0.092 0.031 8.60 < 0.01 1.093(1.028~1.162) 表 4 IL-1β、Caplain-2与心脏彩超结果的相关性分析
指标 IL-1β Caplain-2 r P r P LAD 0.321 < 0.01 0.358 < 0.01 LVDd 0.283 < 0.01 0.342 < 0.01 LVEF -0.288 < 0.01 -0.288 < 0.01 FS -0.334 < 0.01 -0.378 < 0.01 -
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