中国血液净化 ›› 2018, Vol. 17 ›› Issue (02): 88-92.doi: 10.3969/j.issn.1671-4091.2018.02.004

• 临床研究 • 上一篇    下一篇

血液透析患者血浆血栓调节蛋白水平与炎症因子及颈动脉粥样硬化的关系

赵俊丽1,邵霞1,朱君君1,顾敏1,顾秀清1   

  1. 1. 上海市浦东新区周浦医院肾内科
  • 收稿日期:2017-08-07 修回日期:2017-12-20 出版日期:2018-02-12 发布日期:2018-02-12
  • 通讯作者: 赵俊丽 zhaojunli1203@126.com E-mail:zhaojunli1203@126.com
  • 基金资助:

    上海市浦东新区卫生和计划生育委员会卫生计生科技项目(PW2015A-22)

The correlation of plasma thrombomodulin level to inflammatory cytokines and carotid atherosclerosis in maintenance hemodialysis patients

  • Received:2017-08-07 Revised:2017-12-20 Online:2018-02-12 Published:2018-02-12

摘要: 目的探讨维持性血液透析(maintenance hemodialysis, MHD)患者血栓调节蛋白(thrombo?modulin, Tm)水平与细胞因子及颈动脉粥样硬化的关系。方法选择透析龄≥3 个月的MHD 患者102 例(MHD 组)和健康对照组40 例为对象,ELISA 法检测Tm、白介素-1β(interleukin-1beta,IL-1β)、白介素-6(interleukin-6,IL-6)及肿瘤坏死因子-α(tumor necrosis factor-alpha,TNF-α)水平;彩色多普勒超声检查颈动脉病变。采用直线相关与多元逐步Logistic 回归分析Tm 水平与细胞因子及颈动脉病变的关系。结果MHD 组Tm 水平显著高于健康对照组[(16.06±6.68) mg/L 比(5.45±2.14)mg/L,t=10.015,P<0.001]。与健康对照组比较MHD 组IL-1β(t=6.455,P<0.001)、IL-6(t=5.650,P<0.001)、TNF-α(t=7.252,P<0.001)、C 反应蛋白(C-reactive protein,CRP)(t=4.588,P<0.001)水平均显著升高。MHD 组患者颈动脉内中膜厚度(intima-media thickness,IMT)[(1.15±0.21)mm 比(0.78±0.28)mm,t=5.732,P<0.001]、斑块形成率[59.8%比2.5%, χ2=37.747, P<0.001]、颈动脉硬化率[77.45% 比10.00%, χ2=52.631, P<0.001]均显著高于健康对照组。Person 相关分析显示MHD 组Tm 水平与IL-1β (r=0.296, P=0.004)、IL-6(r=0.328, P=0.001)、TNF-α(r=0.288, P=0.005)、CRP(r=0.287, P=0.005)、IMT(r=0.585, P=0.003)、斑块形成率(r=0.498, P=0.005)、颈动脉硬化率(r=0.588, P<0.001)均呈正相关;与收缩压(r=0.267, P=0.003)、舒张压(r=0.189, P=0.035)、年龄(r=0.278, P=0.028)呈正相关。多因素logistic回归分析显示Tm(OR=1.166, 95% CI 1.042~1.305, P=0.008)、IL- 1β(OR=1.005, 95% CI1.000~1.009, P=0.030)、IL-6(OR=1.025, 95% CI 1.006~1.212, P=0.018)、收缩压(OR=1.040,95% CI1.010~1.219,P=0.023)和年龄(OR=1.036,95% CI 1.467~2.009,P=0.019)是MHD 颈动脉病变的独立危险因素。结论MHD 患者Tm 水平显著升高,与IL-6、CRP 等微炎性反应指标及颈动脉病变呈正相关,Tm 是患者并发动脉硬化的危险因素标志物。

关键词: 血液透析, 血栓调节蛋白, 细胞因子, 动脉粥样硬化

Abstract: Objective To investigate the plasma thrombomodulin (Tm) level and to explore its correlation to inflammatory cytokines and carotid atherosclerosis in maintenance hemodialysis (MHD) patients. Methods A total of 102 stable MHD patients undergoing hemodialysis for at least three months as well as 40 healthy controls were enrolled in the study. Blood levels of Tm, IL-1β, IL-6 and TNF-α were determined by ELISA. Serum levels of ceratinine, triglycerides, cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, albumin, hemoglobin and C-reactive protein (CRP) were measured by routine methods. The intima-media thickness (IMT) of bilateral common carotid arteries and atheromatous plaque in carotid arteries were measured by high-resolution ultrasonography. Correlation analyses of Tm with cytokines, atherosclerosis and other parameters were performed. Results Plasma Tm level (16.06 ± 6.68mg/L vs. 5.45 ± 2.14mg/L, t=10.015, P<0.001), and serum levels of IL-1β (t=6.455, P<0.001), IL-6 (t=5.650, P<0.001), TNF-α (t=7.252, P<0.001) and CRP (t=4.588, P<0.001) were significantly higher in MHD patients than in healthy controls. The prevalence of atheromatous plaques and the IMT value of carotid arteries increased significantly in MHD patients as compared with those in healthy controls. Plasma Tm level was higher in MHD patients with carotid atherosclerosis than in patients without carotid atherosclerosis (t=7.034, P<0.001). Tm was positively correlated to IL-1β (r=0.296, P=0.004), IL-6 (r=0.328, P=0.001), TNF-α (r=0.288, P=0.005), CRP (r=0.287, P=0.005), IMT (r=0.585, P=0.003) and carotid atherosclerosis (r=0.588, P<0.001). Multiple stepwise regression analyses showed that Tm (OR=1.166, 95% CI 1.042~1.305, P=0.008), IL- 1β (OR=1.005, 95% CI 1.000~1.009, P=0.030), IL-6 (OR=1.025, 95% CI 1.006~1.212, P=0.018), SBP (OR=1.040,95% CI 1.010~1.219, P=0.023) and age (OR=1.036, 95% CI 1.467~2.009, P=0.019) were the independent risk factors for carotid atherosclerosis in MHD patients. Conclusion Plasma Tm level is significantly higher in MHD patients and is positively correlated with IL-1β, IL-6, TNF-α, CRP, and carotid atherosclerosis, indicating that Tm is an independent risk factor for carotid atherosclerosis in MHD patients. Plasma Tm may be used as a marker to evaluate endothelial damage.

Key words: Hemodialysis, Thrombomodulin, Cytokine, Atherosclerosis