慢性肾脏病非透析患者血清miR-129、miR-205水平变化与血管钙化的关系

Relationship between serum expressions of miR-129 and miR-205 and vascular calcification in patients with chronic kidney disease without dialysis

目的探讨慢性肾脏病(chronic kidney disease,CKD)非透析患者血清miR-129、miR-205表达水平与血管钙化的关系。方法选取2020年6月至2021年1月就诊于河北医科大学第四医院的54例CKD患者为研究对象,按照冠状动脉钙化积分结果分为无钙化组(n=21)与钙化组(n=33),定量PCR法检测两组患者血清miR-129、miR-205和Runx2的表达水平,对两组间的临床资料进行比较,Spearman相关分析评价miR-129、miR-205、Runx2与血管钙化的相关性,采用Logistic回归分析血管钙化发生的危险因素,ROC曲线分析miR-129、miR-205、Runx2单独及联合检测在CKD患者血管钙化中的诊断价值。结果使用在线工具TargetScan靶向预测与Runx2相关的miRNAs(http://www.targetscan.org),结果表明miR-129、miR-205与Runx2存在潜在的结合位点。钙化组血清miR-129、miR-205水平低于无钙化组,Runx2水平高于无钙化组(P<0.05)。Spearman相关性分析表明miR-129(r=-0.445,P<0.05)、mir-205(r=-0.560,P<0.05)表达与血管钙化呈负相关,Runx2表达与血管钙化呈正相关(r=0.28,P<0.05)。Logistic回归分析示高龄、高血磷水平、低水平的miR-129和miR-205是血管钙化发生的独立危险因素。ROC曲线分析显示miR-129、miR-205、Runx2诊断血管钙化的ROC曲线下面积(AUC)分别为0.763、0.831、0.666,两两联合检测的AUC分别为miR_(129+205)=0.856,miR-129+Runx2=0.798,miR-205+Runx2=0.823,三者联合检测的AUC为0.851。结论CKD非透析患者血清miR-129、miR-205表达与血管钙化水平相关,miR-129、miR-205低表达是血管钙化发生的独立危险因素,miR-129、miR-205有望成为CKD非透析患者血管钙化的潜在生物标志物。

Objective To explore the relationship between serum levels of miR-129 and miR-205 and vascular calcification in non-dialysis patients with chronic kidney disease(CKD).Methods From June 2020 to January 2021,54 CKD inpatients were selected as research subjects.According to the scores of coronary artery calcification,they were divided into two groups of non-calcification(n=21)and calcification(n=33).The serum levels of miR-129,miR-205 and Runx2 of two groups were detected by quantitative polymerase chain reaction(PCR).The relevant clinical data between two groups were compared.Spearman’s correlation analysis was performed for evaluating the correlations between miR-129,miR-205,Runx2 and vascular calcification.Logistic regression analysis was employed for analyzing the risk factors of vascular calcification.And receiver operating characteristic(ROC)curve was plotted for examining the diagnostic values of miR-129,miR-205 and Runx2 alone and in combinations in diagnosing vascular calcification in CKD patients.Results The online tool TargetScan(http://www.targetscan.org)was used for targeting and predicting Runx2-related miRNAs.The results hinted at potential binding sites of miR-129,miR-205 and Runx2.Serum levels of miR-129 and miR-205 were lower in calcification group than those in non-calcification group.And Runx2 level was higher than that in non-calcification group(P<0.05).Spearman’s correlation analysis indicated that the expressions of miR-129(r=-0.445,P<0.05)and miR-205(r=-0.560,P<0.05)were negatively correlated with vascular calcification while expression of Runx2 positively correlated with vascular calcification(r=0.28,P<0.05).Logistic regression analysis showed that advanced age,high phosphorus and low levels of miR-129 and miR-205 were independent risk factors for vascular calcification.ROC curve analysis showed that the area under the ROC curve(AUC)of miR-129,miR-205 and Runx2 for diagnosing vascular calcification were 0.763,0.831 and 0.666 respectively.AUC of pairwise combination was miR_(129+205)=0.856,miR-129+Runx2=0.798 and miR-205+Runx2=0.823;AUC of triple combination 0.851.Conclusion The serum expressions of miR-129 and miR-205 are correlated with the extent of vascular calcification in non-dialysis CKD patients.Low miR-129/miR-205 is an independent risk factor for vascular calcification.Both factors are expected to become potential biomarkers for vascular calcification in non-dialysis CKD patients.