维持性血液透析患者循环微小RNA-155、程序性细胞死亡因子4表达与钙磷代谢紊乱的关系

Relationship between serum levels of miR-155 and programmed cell death 4(PDCD4)and disorder of calcium and phosphorus metabolism in maintenance hemodialysis patients

目的探讨维持性血液透析(maintenance hemodialysis,MHD)患者血清微小RNA-155(microRNA-155,miR-155)、程序性细胞死亡因子4(programmed cell death 4,PDCD4)表达与钙磷代谢紊乱的关系。方法选取2018年9月-2020年10月于三河市燕郊人民医院行MHD≥3个月且病情控制稳定的慢性肾脏病患者86例为研究组,同期选择体检的健康人群80例为对照组。利用酶联免疫吸附法检测血清PDCD4、高敏C反应蛋白(hs-CRP)水平,全自动生化分析仪检测血清白蛋白、血红蛋白、血钙、血磷、全段甲状旁腺激素(iPTH)水平,荧光定量PCR技术检测血清miR-155水平,分析研究组与对照组的一般资料信息,比较研究组和对照组血清miR-155、PDCD4水平差异。根据MHD患者年龄、透析龄、透析频率进行分组,比较各组血清miR-155、PDCD4水平。以血清miR-155、PDCD4水平均值为分界点分为高表达组和低表达组,分析各组MHD患者钙磷代谢情况。利用多因素Logistic回归分析影响MHD患者发生钙磷代谢紊乱的危险因素。结果研究组血清白蛋白水平低于对照组(t=8.848,P<0.001),血磷、iPTH、hs-CRP、miR-155、PDCD4水平均高于对照组(t值分别为10.491、3.578、10.988、16.298、19.419,P值分别为<0.001、<0.001、<0.001、<0.001、<0.001);年龄≥60岁、透析龄≥3年、透析频率>2次/w的MHD患者血清miR-155、PDCD4水平均分别高于年龄<60岁、透析龄<3年、透析频率2次/w的MHD患者(t值分别为13.723、7.773、4.846、15.740、10.206、5.154,P值分别为<0.001、<0.001、<0.001、<0.001、<0.001、<0.001);miR-155和PDCD4高表达组患者血钙、血磷、iPTH达标患者比例均分别低于miR-155和PDCD4低表达组患者,miR-155、PDCD4表达情况与血钙、血磷、iPTH水平有关(Z值分别为=21.333、7.898、7.407、15.712、9.234、7.899,P值分别为<0.001、0.019、0.025、<0.001、0.010、0.019);多因素Logistic回归分析结果显示,血清白蛋白(OR=2.431,95%CI:1.388-4.258,P=0.002)、miR-155(OR=2.715,95%CI:1.433-5.144,P=0.002)、PDCD4(OR=2.629,95%CI:1.429-4.836,P=0.002)是影响MHD患者钙磷代谢紊乱的独立危险因素。结论MHD患者血清miR-155、PDCD4水平与血钙、血磷、iPTH代谢有关,高水平的miR-155、PDCD4是影响MHD患者钙磷代谢紊乱的独立危险因素。

Objective To investigate the relationship between serum levels of microRNA-155(miR-155)and programmed cell death 4(PDCD4)and disorder of calcium and phosphorus metabolism in maintenance hemodialysis(MHD)patients.Methods A total of 86 MHD patients treated during September 2018 to October 2020 in Yanjiao People's Hospital of Sanhe City for more than 3 months and with stable conditions were recruited as the study group,and 80 healthy people for physical check-up in our hospital were selected as the control group.Serum PDCD4 and high-sensitivity C-reactive protein(hs-CRP)were assayed by ELISA,hemoglobin and serum albumin,calcium,phosphorus and intact parathyroid hormone(iPTH)were detected by automatic biochemical analyzer,and serum miR-155 was determined by fluorescence quantitative PCR.General information of the patients was analyzed.Serum miR-155 and PDCD4 levels were compared between the study group and the control group.The MHD patients were further divided into subgroups based on age,dialysis vintage and dialysis frequency,and serum miR-155 and PDCD4 levels were then compared among the subgroups.The MHD could be further grouped into the high expression group and the low expression group based on their average serum miR-155 and PDCD4 levels;calcium and phosphorus metabolism were then analyzed between the two groups.Logistic regression analysis was used to evaluate the risk factors for calcium and phosphorus metabolism disorder in MHD patients.Results Serum albumin was significantly lower in the study group than in the control group(t=8.848,P<0.001),but serum phosphorus,iPTH,hs-CRP,miR-155,and PDCD4 levels were significantly higher in the study group than in the control group(t=10.491,3.578,10.988,16.298 and 19.419 respectively;P<0.001).Serum miR-155 and PDCD4 levels were higher in the MHD patients with age≥60 years,dialysis vintage≥3 years and dialysis frequency>2 times/week than those with age<60 years,dialysis vintage<3 years and dialysis frequency 2 times/week(t=13.723,7.773,4.846,15.740,10.206 and 5.154,respectively;P<0.001).The compliance rates of serum calcium,phosphorus and iPTH were lower in the high expression group than in the low expression group.The expression levels of miR-155 and PDCD4 were correlated with the serum levels of calcium,phosphorus and iPTH(Z=21.333,7.898,7.407,15.712,9.234 and 7.899,respectively;P<0.001,0.019,0.025,<0.001,0.010 and 0.019,respectively).Multivariate logistic regression analysis showed that serum albumin(OR=2.431,95%CI:1.38-4.258,P=0.002),miR-155(OR=2.715,95%CI:1.433-5.144,P=0.002)and PDCD4(OR=2.629,95%CI:1.429-4.836,P=0.002)were the independent risk factors for calcium and phosphorus metabolism disorder in MHD patients(P<0.05).Conclusion Serum miR-155 and PDCD4 levels were correlated with calcium and phosphorus metabolism and iPTH in MHD patients.High serum levels of miR-155 and PDCD4 were the independent risk factors for calcium and phosphorus metabolism disorder in MHD patients.