血清骨保护素及相关炎症因子在冠心病患者中的表达及意义

Expression and significance of serum osteoprotegerin and related inflammatory factors in patients with coronary heart disease

目的探讨血清骨保护素及相关炎症因子在冠心病患者中的表达及意义。方法按照病例对照研究方法,选取2018年3月至2019年7月间新乡医学院附属南阳市第二人民医院收治胸痛患者236例研究对象,根据冠状动脉造影检查结果分为冠心病组132例,对照组(非冠心病的患者)104例。问卷调查收集患者一般资料;抽取患者清晨空腹外周静脉血5 mL,离心收集血清,酶联免疫吸附试验法检测骨保护素、可溶性受体激活的核因子κB(monoclonal antibody to receptor activator of nuclear factor kappa B,RANK)配体、白细胞介素6(interleukin 6,IL-6)、C反应蛋白、胰岛素样生长因子1(insulin-like growth factor 1,IGF-1)、单核细胞趋化因子1(monocyte chemoattractant protein 1,MCP-1)、基质金属蛋白酶9(matrix metalloproteinase 9,MMP-9)浓度。结果冠心病组患者血清骨保护素、IL-6、C反应蛋白、IGF-1、MCP-1、MMP-9浓度分别为(1.85±0.49)μg/L、(65.93±5.18)ng/L、(15.74±2.52)mg/L、(725.19±13.36)μg/L、(302.16±15.92)μg/L、(58.31±7.94)μg/L均明显高于对照组(1.42±0.44)μg/L、(47.56±3.51)ng/L、(1.91±0.67)mg/L、(228.61±12.05)μg/L、(246.39±10.28)μg/L、(37.09±4.76)μg/L,可溶性RANK配体(332.69±14.91)ng/L明显低于对照组(380.85±19.56)ng/L,差异有统计学意义(t值分别为4.739、21.065、29.721、27.637、18.911、16.463、17.085,P均<0.05)。血清骨保护素、IL-6、C反应蛋白、IGF-1浓度在不同病变支数组之间比较差异均有统计学意义(P均<0.05);其中三支病变组(2.05±0.51)μg/L、(80.96±25.70)ng/L、(19.79±2.03)mg/L、(849.07±18.95)μg/L明显高于双支病变组(1.83±0.45)μg/L、(62.74±20.61)ng/L、(13.82±1.75)mg/L、(714.84±19.06)μg/L和单支病变组(1.61±0.42)μg/L、(53.09±18.37)ng/L、(9.67±1.40)mg/L、(507.51±17.83)μg/L,双支病变组明显高于单支病变组,差异有统计学意义(P均<0.05)。多因素非条件Logistic回归分析显示,血清骨保护素、IGF-1是冠心病发病的影响因素。ROC曲线分析显示,血清骨保护素的曲线下面积(area under curve,AUC)为0.827,在最佳临界点1.54μg/L时,诊断的敏感度为84.09%(111/132),特异度为73.48%(97/132);血清IGF-1的AUC为0.883,在最佳临界点395.78μg/L时,诊断的敏感度为71.21%(94/132),特异性为96.21%(127/132)。结论血清骨保护素及相关炎性因子IGF-1是冠心病发生的影响因素,与冠状动脉病变严重程度呈正相关,对冠心病的发生有较好的诊断价值。

Objective To investigate the expression and significance of serum osteoprotegerin and related inflammatory factors in patients with coronary heart disease.Methods According to case-control study method,236 subjects with chest pain admitted to Nanyang Second General Hospital Affiliated to Xinxiang Medical University from March 2018 to July 2019 were collected.According to the results of coronary angiography,they were divided into 132 cases of coronary heart disease group and control group(non-coronary Patients with heart disease)104 cases.Questionnaire survey to collect general data of patients;5 mL of fasting peripheral venous blood was collected in the morning,and serum was collected by centrifugation.Enzyme-linked immunosorbent assay was used to detect osteoprotegerin and monoclonal antibody to receptor activator of nuclear factor kappa B(RANK)ligand,interleukin 6(IL-6),C-reactive protein,insulin-like growth factor 1(IGF-1),monocyte chemoattractant protein 1(MCP-1),matrix metalloproteinase 9(MMP-9)levels.Results The levels of serum osteoprotegerin,IL-6,C-reactive protein,IGF-1,MCP-1,and MMP-9 in patients with coronary heart disease were(1.85±0.49)μg/L,(65.93±5.18)ng/L,(15.74±2.52)mg/L,(725.19±13.36)μg/L,(302.16±15.92)μg/L and(58.31±7.94)μg/L,respectively,which were significantly higher than those in control group(1.42±0.44)μg/L,(47.56±3.51)ng/L,(1.91±0.67)mg/L,(228.61±12.05)μg/L,(246.39±10.28)μg/L and(37.09±4.76)μg/L.Soluble RANK ligand(332.69±14.91)ng/L was significantly lower than the control group(380.85±19.56)ng/L.The difference was statistically significant(t value were 4.739,21.065,29.721,27.637,18.911,16.463 and 17.085,respectively,all P<0.05).The levels of serum osteoprotegerin,IL-6,C-reactive protein,and IGF-1 were statistically significant among different lesion groups(all P<0.05).The levels of osteoprotegerin,IL-6,C-reactive protein and IGF-1 in three vessel disease group((2.05±0.51)μg/L,(80.96±25.70)ng/L,(19.79±2.03)mg/L,(849.07±18.95)μg/L)were significantly higher than the double-vessel disease group((1.83±0.45)μg/L,(62.74±20.61)ng/L,(13.82±1.75)mg/L,(714.84±19.06)μg/L)and single-vessel disease group((1.61±0.42)μg/L,(53.09±18.37)ng/L,(9.67±1.40)mg/L,(507.51±17.83)μg/L),and the double-vessel disease group was significantly higher than the single-vessel disease group,the difference was statistically significant(all P<0.05).Multivariate unconditional Logistic regression analysis showed that serum osteoprotegerin and IGF-1 are the influencing factors of coronary heart disease.ROC curve analysis showed that the AUC of serum osteoprotegerin was 0.827.At the best cut-off point of 1.54μg/L,the diagnostic sensitivity was 84.09%(111/132)and the specificity was 73.48%(97/132);the AUC of serum IGF-1 was 0.883,which was at the best cut-off point.At 395.78μg/L,the diagnostic sensitivity was 71.21%(94/132)and the specificity was 96.21%(127/132).Conclusion Serum osteoprotegerin and related inflammatory factor IGF-1 are influential factors in the occurrence of coronary heart disease,and are positively correlated with the severity of coronary artery disease,and have a good diagnostic value for the occurrence of coronary heart disease.