儿童1型糖尿病外周血中微小RNA-155和T细胞免疫球蛋白黏蛋白分子3的表达关系及临床意义

Expression and clinical significance of miR-155 and Tim-3 in peripheral blood of children with type 1 diabetes mellitus

目的分析儿童T1DM患者外周血微小RNA 155(miR-155)、T细胞免疫球蛋白黏蛋白分子3(Tim-3)的表达及临床意义。方法选取2015年9月至2018年6月住院治疗的65例儿童T1DM患者作为研究对象(T1DM组),同期选取儿童体检正常者64名为正常对照(NC)组。采用qRT-PCR法检测血清miR-155及单核细胞中miR-155、Tim-3表达水平,Pearson相关性分析血清miR-155、单核细胞miR-155、Tim-3及临床指标的相关性,应用ROC曲线分析血清miR-155、单核细胞miR-155对儿童T1DM的预测作用。结果与NC组相比,T1DM组HbA1c、FPG、白介素2(IL-2)、γ干扰素(IFN-γ)、IL-4、IL-5水平和Tim-3表达水平均升高(P<0. 05),血清、单核细胞miR-155表达水平降低(P<0. 05);相关性分析显示,血清、单核细胞miR-155与FPG、HbA1c、IFN-γ呈负相关(r=-0. 476、-0. 515、-0. 559、-0. 755、-0. 684、-0. 632,P<0. 05);Tim-3与FPG、HbA1c、IL-2、IFN-γ呈正相关(r=0. 724、0. 657、0. 545、0. 611,P<0. 05);血清miR-155与单核细胞miR-155表达呈正相关(r=0. 592,P<0. 05);单核细胞miR-155与Tim-3表达水平呈负相关(r=-0. 613,P<0. 05);ROC曲线分析结果显示,血清miR-155曲线下面积为0. 797(敏感度为87. 5%,特异度为79. 5%),单核细胞预测T1DM曲线下面积为0. 876(敏感度为87. 5,特异度为86. 2%)。结论儿童T1DM患者外周血血清及单核细胞中miR-155低表达、Tim-3高表达,二者呈负相关,miR-155可能通过调控Tim-3表达参与儿童T1DM的发生发展,其血清miR-155可能作为临床诊断治疗儿童T1DM的潜在靶点。

Objective To analyze the expression and clinical significance of microRNA 155(miR-155 and T cell immunoglobulin and mucin molecule 3(Tim-3)in peripheral blood of children with type 1 diabetes mellitus(T1 DM).Methods65 children with T1 DM were selected from Sep. 2015 to Jun. 2018. 64 healthy persons were selected as controls. Serum miR-155 and the expressions of miR-155 and Tim-3 in monocytes were detected by qRT-PCR. The correlations between serum miR-155,monocyte miR-155 and Tim-3 expression and clinical related indicators were analyzed by Pearson analysis. The predictive effects of serum miR-155 and monocyte miR-155 on T1 DM children were analyzed by ROC curve.ResultsCompared with healthy control group,the levels of HbA1 c,FPG,IL-2,IFN-γ,IL-4,IL-5 and Tim-3 in T1 DM group increased significantly(P<0. 05),and the levels of serum and monocyte miR-155 decreased significantly(P<0. 05). Serum and monocyte miR-155 were negatively correlated with FPG,HbA1 c and IFN-γ(r=-0. 476,-0. 515,-0. 559,-0. 755,-0. 684 and-0. 632,P<0. 05.)Tim-3 was positively correlated with FPG,HbA1 c,IL-2,IL-2 and IFN-γ(r=0. 724,0. 657,0. 545 and 0. 611,P<0. 05). Serum miR-155 was positively correlated with the expression of miR-155 in monocyte(r=0. 592,P<0. 05).The expression level of miR-155 in monocyte was negatively correlated with Tim-3(r=-0. 613,P<0. 05). Analysis results showed that the area under the serum miR-155 ROC curve was 0. 797(sensitivity87. 5%,specificity 79. 5%). The area under the monocyte miR-155 ROC curve predicted T1 DM was 0. 876(sensitivity 87. 5,specificity 86. 2%).ConclusionLow expression of miR-155 and high expression of Tim-3 in peripheral blood serum and monocytes were observed in T1 DM children. MiR-155 may participate in the process of diabetes by regulating the expression of Tim-3. Serum miR-155 may be an important target for clinical diagnosis and treatment of T1 DM children.