维持性血液透析患者外周血单个核细胞核因子κB活性与微炎症、氧化应激状态及心血管疾病的关系

摘要

目的:探讨维持性血液透析(MHD)患者外周血单个核细胞(PBMC)核因子κB (NF-κB)活性与微炎症、氧化应激状态及心血管疾病(CVD)的关系. 方法:选取MHD治疗3个月以上的患者(32例),以体检健康者(12例)为对照组.采用ELISA法检测受试者PBMC的NF-κB活性,比色法检测血清总抗氧化能力(TAOC)及丙二醛(MDA).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.二分类Logistic回归分析NF-κB活性与CVD的关系. 结果:MHD患者PBMC的NF-κB活性[(1 142.4±413.0)ng/mg核蛋白vs(208.3±39.5) ng/mg核蛋白,P＜0.05]、血清高敏C反应蛋白(hsCRP)(3.2 mg/L vs0.5 mg/L,P＜0.05)、TAOC[ (21.9±6.6)U/ml vs (15.7±2.3)U/ml,P＜0.05]和MDA[ (6.80±0.86) nmol/ml vs (3.89±0.51) nmol/ml,P＜0.05]皆显著高于对照组.单次HD后MHD患者PBMC的NF-κB活性显著升高[(2 076.5±690.1)ng/mg核蛋白vs(1 142.2 ±413.0)ng/mg核蛋白,P＜0.05],TAOC显著降低[(13.6±5.0) U/ml vs(21.9±6.6)U/ml,P＜0.05].Pearson相关分析显示PBMC的NF-κB活性与白细胞计数(r=0.454,P＜0.05)、血清hsCRP(r =0.590,P＜0.05)及MDA(r=0.390,P＜0.05)呈正相关.线性回归分析显示白细胞计数(β=0.338,P＜0.05)、血清hsCRP(β =0.440,P＜0.05)及MDA(β=0.319,P＜0.05)皆与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(＞1 170.0 ng/mg核蛋白)是CVD的独立危险因素(OR=8.47,P＜0.05). 结论:MHD患者PBMC的NF-κB活性显著升高,且与微炎症、氧化应激状态及CVD相关,可作为患者的炎症标志物.%Objective:The aim of the study was to measure nuclear factor kappa B ( NF-Kb) activity of peripheral blood mononuclear cell (PBMC) and evaluate the correlation of NF-Kb activity and microinflammation, oxidative stress and cardiovascular disease in patients with maintenance hemodialysis (MHD). Methodology: The peripheral blood was obtained from thirty two patients with MHD before and after undergoing hemodialysis and 12 age-matched healthy subjects regarded as control. Nuclear extracts NF-Kb activity of PBMC was measured by enzyme-linked immunosorbant assay (ELISA) and serum total antioxidant capacity (TAOC) and malondialdehyde (MDA) was measured by colorimetry. 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 correlation of NF-Kb activity and CVD in MHD patients. Results:NF-KB activity of PBMC [ ( 1 142 ± 413 ) ng/mg nuclear extracts vs (2 083 ± 39. 5 ) ng/mg nuclear extracts, P<0.05], serum hsCRP(3.2 mg/L vs 0.5 mg/L,P < 0. 05), TAOC[(21.9 ±6.6)U/ml vs (15.7 ±2.3)U/ml,P<0.05]and MDA[(6.80 ± 0. 86) nmol/ml vs (3.89 ±0.51) nmol/ml,P < 0.05 ] were significantly higher in MHD patients compared with controls. After a single HD session, NF-Kb activity of PBMC was increased acutely [ post-HD (2 077 ± 690) ng/mg nuclear extracts vs pre-HD (1 142 ± 413 ) ng/mg nuclear extracts, P < 0. 05 ] and T-AOC was decreased significantly(13. 6 ±5.0 U/ml vs 21.9 ±6.6 U/ml, P < 0.05). In all MHD patients, NF-Kb activity was correlated positively with white blood cell count(r=0.454,P<0.05) ,hsCRP(r=0. 590,P<0. 05) and MDA(r = 0. 390, P < 0.05). Linear regression analysis showed white blood cell count ( p = 0. 338, P < 0. 05 ) , hsCRP ( p = 0.440, P< 0.05) and MDA(p = 0. 319, P < 0.05) were independently associated with NF-Kb activity. High NF-Kb activity ( > 1 170 ng/mg nuclear extracts) was positively and independently associated with CVD ( OR = 8.47, P < 0.05). Conclusion:NF-Kb activity of PBMC is markedly elevated in MHD patients, which is associated with microinflammation, oxidative stress and cardiovascular disease and can be a useful marker of inflammation in patients with MHD.