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

NF-κB activity of peripheral blood mononuclear cell,microinflammation,oxidative stress and cardiovascular disease in hemodialysis patients

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[(1142.4±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)(3.2mg/Lvs0.5mg/L,P<0.05)、TAOC[(21.9±6.6)U/mlvs(15.7±2.3)U/ml,P<0.05]和MDA[(6.80±0.86)nmol/mlvs(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[(2076.5±690.1)ng/mg核蛋白vs(1142.2±413.0)ng/mg核蛋白,P<0.05],TAOC显著降低[(13.6±5.0)U/mlvs(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(>1170.0ng/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-κB） activity of peripheral blood mononuclear cell （PBMC） and evaluate the correlation of NF-κB activity and mieroinfiammation, 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 alter undergoing hemodialysis and 12 age-matched healthy subjects regarded as control. Nuclear extracts NF-κB activity of PBMC was measured by enzyme-linked immunosorbant assay （ELISA） and serum total antioxidant capacity （TAOC） and malondialdehyde （MDA） was measured by eolorimetry. Pearson correlation and linear regression were used to assess the relationship between NF-κB activity and other laboralory parameters. Binary logistic regression was used to assess the correlation of NF-κB activity and CVD in MHD patients. Results：NF-κB activity of PBMC [ （1 142 ± 413 ）ng/mg nuclear extracts vs （2 083 ± 39.5 ）ng/mg nuclear extracls, 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-κB 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 （ β = 0. 338, P 〈 0. 05 ）, hsCRP （ β= 0. 440, P〈0. 05）and MDA（ β= 0. 319,P 〈 0.05） were independently associated with NF-KB activity. High NF-κB activity （ 〉 1 170 ng/mg nuclear extracts） was positively and independently associated with CVD （ OR = 8. 47, P κ 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.