维持性血液透析(MHD)患者外周血单个核细胞NF-κB活性与心血管疾病(CVD)相关

摘要

Objective To measure the nuclear factor kappa B (NF-kB) activity of peripheral blood mononuclear cell (PBMC) and to observe the relationship between NF-kB activity and cardiovascular disease (CVD) in maintenance hemodialysis (MHD) patients. Methods Blood was obtained from 32 MHD patients before and after undergoing hemodialysis and 12 age-matched healthy subjects. Nuclear extracts NF-kB activity of PBMC and plasma pentraxin3 (PTX3) were measured by enzyme-linked immunosorbant assay (ELISA). Pearson correlation and linear regression were used to assess the relationship between NF-kB activity and other laboratory parameters. Binary logistic regression was used to assess the association of NF-kB activity and CVD in MHD patients. Receiver operating characteristic (ROC) curves were used to assess the association with NF-kB activity, PTX3, high sensitive C-reactive protein (hsCRP) and CVD in MHD patients. Results NF-kB activity of PBMC,PTX3 and hsCRP were significantly higher in MHD patients compared with controls. After a single HD session NF-kB activity of PBMC and PTX3 increased acutely. Patients with CVD had higher NF-kB activity than non-CVD patients. In all MHD patients NF-kB activity correlated positively with white blood cell count (r = 0. 454, P = 0. 009) , hsCRP ( r = 0. 590, P<0. 001) , PTX3(r=0. 680, P<0. 001), cardiac troponin T (r = 0. 409, P = 0. 020) and carotid artery intima-media thickness (r= 0. 541 ,P = 0. 011). Linear regression analysis showed that white blood cell count (β= 0. 338, P=0. 028),hsCRP (β=0. 440, P= 0.005 ),PTX3 (β= 0. 487,P= 0. 004) and carotid artery intima-media thickness (β= 0. 453, P = 0. 032) were independently associated with NF-kB activity. High NF-kB activity was positively and independently associated with CVD (OR = 8. 47,P= 0. 022). ROC curves analysis showed the association between NF-kB activity and CVD was more closely than PTX3 and hsCRP. The areas under the curve for NF-kB activity, PTX3 and hsCRP were 0. 791 (95 % CI 0. 633 - 0. 950, P = 0. 006) , 0. 785 (95%CI 0. 628 - 0. 943, P = 0. 007) and 0. 711 (95% CI 0.514-0.907, P = 0. 046), respectively. Conclusions NF-kB activity of PBMC is markedly elevated in MHD patients; hemodiaysis (HD) procedure induces NF-kB activation) NF-kB activity of PBMC is associated with CVD and could be a useful marker of inflammation and risk factor of CVD in MHD patients.%目的 探讨维持性血液透析( maintenance hemodialysis,MHD)患者外周血单个核细胞(peripheral blood mononuclear cell,PBMC)核因子-κB(nuclear factor kappa B,NF-κB)活性与心血管疾病(cardiovascular disease,CVD)的关系.方法 选取MHD治疗3个月以上的稳定患者(n=32),以体检健康人为对照组(n=12),采用酶联免疫吸附法检测受试者PBMC的NF-κB活性及血浆五聚素3(pentraxin 3,PTX3).用Pearson相关和线性回归分析PBMC的NF-κB活性与其他指标的相关性.用二分类Logistic回归分析PBMC的NF-κB活性与CVD的关系.用受试者工作特征(receiver operating characteristic,ROC)曲线比较PBMC的NF-κB活性、PTX3和高敏C反应蛋白(high sensitivity C-reactive protein,hsCRP)与CVD的相关性.结果 MHD患者PBMC的NF-κB活性、血浆PTX3和血清hsCRP皆显著高于对照组；单次透析后MHD患者PBMC的NF-κB活性和血浆PTX3显著升高；合并CVD患者PBMC的NF-κB活性显著高于非CVD患者.Pearson相关分析显示PBMC的NF-κB活性与白细胞计数(r=0.454,P=0.009)、血清hsCRP(r=0.590,P＜0.001)、血浆PTX3(r=0.680,P＜0.001)、心肌肌钙蛋白T(r=0.409,P=0.020)及颈动脉内膜中层厚度(r=0.541,P =0.011)呈显著正相关.线性回归分析显示白细胞计数(β=0.338,P=0.028)、血清hsCRP(β=0.440,P =0.005)、血浆PTX3(β=0.487,P=0.004)及颈动脉内膜中层厚度(β=0.453,P=0.032)与PBMC的NF-κB活性独立相关.Logistic回归分析显示PBMC的NF-κB活性升高是CVD的独立危险因素(OR=8.47,P =0.022).受试者工作特征曲线(receiver operating characteristic curve,ROC曲线)分析显示,PBMC的NF-κB活性与CVD的相关性高于PTX3和hsCRP,三者的ROC曲线下面积分别为0.791(95％CI:0.633～0.950,P=0.006)、0.785(95％CI:0.628～0.943,P=0.007)和0.711(95％CI:0.514～0.907,P=0.046).结论 MHD患者PBMC的NF-κB活性显著升高；血液透析(hemodialysis,HD)过程可激活PBMC的NF-κB; MHD患者PBMC的NF-κB活性与CVD相关,可作为患者炎症和CVD危险因素的标志物.