低钙透析液对维持性血液透析患者微炎症状态的影响及其机制研究

Effects of low calcium dialysate on microinflammatory status and its mechanisms in maintenance hemodialysis patients

目的观察低钙透析液（LCD）对维持性血液透析患者微炎症状态的影响并探讨其机制。方法纳入2015年4-10月暨南大学医学院附属广州市红十字会医院肾内科血液透析中心维持性血液透析患者50例，随机数字表法分为标准钙透析液（SCD，钙浓度1．5mmol／L）组和LCD（钙浓度1．25mmol／L）组，各25例。所有患者入组前均采用SCD进行透析，入组后LCD组改用LCD，SCD组仍予SCD进行透析，研究持续6个月。比较2组患者入组前和人组后3、6个月相关生化指标，比较2组入组前和人组后6个月血液中高敏C反应蛋白（hs-CRP）水平，分析入组前患者hs-CRP与钙磷乘积的相关性。收集透析前后患者外周血单个核细胞（PBMCs），采用蛋白质印迹方法检测PBMCs中钙敏感受体（CaSR）和磷酸化核因子KB（pNF-KB）表达水平。结果LCD组23例、SCD组24例完成研究。人组前2组各相关生化指标及hs-CRP差异无统计学意义（P〉0．05），人组后3和6个月，LCD组血钙明显低于人组前和SCD组同时点[（1．14±0．15）mmol／L比（1．25±0．13）、（1．27±0．16）mmol／L，（1．15±0．14）mmol／L比（1．25±0．13）、（1．28±0．17）mmol／L]，人组后6个月，LCD组钙磷乘积明显低于入组前和SCD组同时点[（50±13）比（58±16）、（59±14）]（P〈0．05）。入组后6个月LCD组患者hs-CRP明显低于人组前及SCD组同时点[（4±3）mg／L比（8±4）、（8±5）mg／L]（P〈0．05）。入组前患者钙磷乘积与hs-CRP呈正相关（r=0．608，P〈0．01）。2组透析患者透析前后PMBCs中CaSR和pNF-κB水平均高于健康志愿者，透析治疗后，LCD组PMBCs中CaSR和pNF-κB水平较透析前及SCD组透析后明显下调。结论在维持性血液透析患者中采用LCD可改善患者微炎症状态，其机制可能为通过减轻钙超载下调PMBCs中CaSR和pNF-κB的表达。

Objective To explore the effects of low calcium dialysate （LCD） on microinflammatory status and the mechanisms in maintenance hemodialysis patients. Methods Fifty patients receiving maintenance hemodialysis from April to October in 2015 were randomly divided into standard calcium dialysate （SCD, Ca2± 1.5 mmoL/L） group and LCD group （Ca2± 1.25 mmol/L） （25 cases in each group）. All patients received SCD before enrolhnent, then received LCD in LCD group and still received SCD in SCD group after enrollment. The research lasted for 6 months. The relative biochemical indexes before, 3 and 6 months after enrollment, the high-sensitivity C-reactive protein （hs-CRP） before and 6 months after enrollment were compared between groups. The correlation of hs-CRP and calcium-phosphorus product was analyzed. The peripheral blood mononuclear cells （PBMCs） were collected before and after hemodialysis, then Western blotting was used to analyze the levels of calcium sensing receptor （CaSR） and nuclear factor-κB （NF-κB） in PBMCs. Results Totally 23 cases in LCD group and 24 cases in SCD group completed the research. The relative biochemical indexes before enrollment were not significantly different between groups （ P 〉 0. 05 ） ; 3 and 6 months after enrollment, the blood calcium in LCD group was significantly lower than that before enrollment and that in SCD group [ （ 1.14 ± 0. 15 ） mmol/L vs （1.25 ±0. 13）, （1.27 ±0. 16） mmoL/L,（1.15 ±0. 14） mmol/L vs （1.25 ±0. 13）, （1.28 ±0. 17） mmol/Ll （ P 〈 0. 05 ） ; 6 months after enrollment, the calcium-phosphorus product was significantly lower than that before enrollment and that in SCD group [ （50 ± 13） vs （58 ± 16） , （59 ± 14） ] （P 〈0.05） ; 6 months after enrollment,the hs-CRP was significantly lower than that before enrollment and that in SCD group [ （4 ± 3 ） mg/L vs （8 ± 4） , （8 ± 5） mg/L ] （ P 〈 0.05 ）. Before enrollment, the calcium-phosphorus product was positively correlated with hs-CRP （ r = 0. 6076, P 〈 0. 01 ）. The CaSR and NF-κB in PBMCs were significantly higher in hemodialysis patients than those in healthy people both before and after hemodialysis; in LCD group, after hemodialysis they were significantly lower than those before hemodialysis and those in SCD group. Conclusion In maintenance hemodialysis patients, LCD can improve microinflammatory status, which is related with inhibition of CaSR and NF-κB expression in PMBCs.