过敏性紫癜患儿血清miR-125b、HIF-1α表达水平及其与Th1/Th2平衡的关系

Relationship between serum miR-125b and HIF-1α expression levels and Th1/Th2 balance in children with allergic purpura

目的检测过敏性紫癜患儿血清microRNA-125b(miR-125b)、缺氧诱导因子-1α(HIF-1α)表达水平,并探讨其与辅助性T细胞1(Th1)/辅助性T细胞2(Th2)(Th1/Th2)平衡的关系。方法选择2021年5月至2022年12月三门峡市中心医院收治的94例过敏性紫癜患儿作为研究组,另选择同期在我院体检的88例健康儿童作为对照组。所有受检者入院后均采用实时荧光定量PCR(qRT-PCR)法检测外周血miR-125b水平,采用酶联免疫吸附试验检测血清HIF-1α、IFN-γ、IL-4水平,利用流式细胞仪检测Th1、Th2细胞水平并计算Th1/Th2比值。采用Pearson相关分析探讨过敏性紫癜患儿血清miR-125b、HIF-1α表达水平与Th1/Th2比值的关系,采用受试者工作特征曲线(ROC)评估血清miR-125b、HIF-1α表达水平对过敏性紫癜发生的预测价值。结果研究组患者的血清miR-125b、HIF-1α及外Th2细胞水平分别为(0.80±0.18)、(122.54±20.54)pg/L、(7.04±1.57),明显高于对照组的(0.38±0.11)、(48.58±8.99)pg/L、(4.22±0.55),Th1细胞水平、Th1/Th2比值分别为(7.55±1.66)、(1.07±0.11),明显低于对照组的(12.01±2.80)、(2.85±0.58),差异均有统计学意义(P<0.05);研究组患者的血清IFN-γ水平为(19.28±2.66)pg/mL,明显低于对照组的(26.64±3.41)pg/mL,血清IL-4水平为(28.44±3.87)ng/L,明显高于对照组的(17.66±2.99)ng/L,差异均有统计学意义(P<0.05);经Pearson相关分析结果显示,过敏性紫癜患儿血清miR-125b与IFN-γ、Th1/Th2比值均呈负相关(r=-0.447、-0.516,P<0.05),与IL-4呈正相关(r=0.521,P<0.05);血清HIF-1α与IFN-γ、Th1/Th2比值均呈负相关(r=-0.511、-0.445,P<0.05),与IL-4呈正相关(r=0.495,P<0.05);经ROC分析结果显示,血清miR-125b预测小儿过敏性紫癜的曲线下面积(AUC)为0.841,敏感度、特异度分别为90.01%、64.41%;HIF-1α预测小儿过敏性紫癜的AUC为0.764,敏感度、特异度分别为90.02%、58.78%;两者联合预测小儿过敏性紫癜的AUC为0.910,敏感度、特异度为88.74%、87.19%。结论过敏性紫癜患儿血清miR-125b、HIF-1α表达水平均升高,且两者与Th1/Th2比值呈负相关,两者可通过调节Th1/Th2、介导炎症反应参与疾病发展,有望作为预测小儿过敏性紫癜发病的有效指标。

Objective To detect the expression levels of serum microRNA-125b(miR-125b)and hypoxia-inducible factor-1α(HIF-1α)in children with allergic purpura,and to explore their relationship with the balance of helper T cell 1(Th1)/helper T cell 2(Th2)(Th1/Th2).Methods A total of 94 children with allergic purpura admitted to Sanmenxia Central Hospital from May 2021 to December 2022 were selected as the study group,and 88 healthy children who underwent physical examination in the Hospital during the same period were selected as the control group.The level of miR-125b in peripheral blood was detected by real-time fluorescent quantitative PCR(qRT-PCR),and the levels of HIF-1α,IFN-γ,and IL-4 in serum were detected by enzyme-linked immunosorbent assay.The levels of Th1 and Th2 cells were detected by flow cytometry,and the Th1/Th2 ratio was calculated.Pearson correlation analysis was used to explore the relationship between the expression levels of serum miR-125b and HIF-1αand Th1/Th2 ratio in children with Henoch-Schonlein purpura.The receiver operating characteristic curve(ROC)was used to evaluate the predictive value of the expression levels of serum miR-125b and HIF-1α for the occurrence of Henoch-Schonlein purpura.Results The levels of serum miR-125b,HIF-1α,and outer Th2 cells in the study group were 0.80±0.18,(122.54±20.54)pg/L,and 7.04±1.57,respectively,which were significantly higher than 0.38±0.11,(48.58±8.99)pg/L,4.22±0.55 in the control group.Th1 cell level and Th1/Th2 ratio were 7.55±1.66 and 1.07±0.11,respectively,significantly lower than 12.01±2.80 and 2.85±0.58 in the control group(P<0.05).The serum IFN-γ level of the study group was(19.28±2.66)pg/mL,which was significantly lower than(26.64±3.41)pg/mL of the control group(P<0.05);the serum IL-4 level was(28.44±3.87)ng/L,which was significantly higher than(17.66±2.99)ng/L of the control group(P<0.05).Pearson correlation analysis showed that serum miR-125b was negatively correlated with IFN-γ and Th1/Th2 ratios(r=-0.447,-0.516,all P<0.05),and positively correlated with IL-4(r=0.521,P<0.05).Serum HIF-1αwas negatively correlated with IFN-γ and Th1/Th2 ratio(r=-0.511,-0.445,all P<0.05),and positively correlated with IL-4(r=0.495,P<0.05).ROC curve analysis showed that the area under the curve(AUC)of serum miR-125b for predicting allergic purpura was 0.841,and the sensitivity and specificity were 90.01%and 64.41%,respectively.AUC of HIF-1α for predicting allergic purpura was 0.764,and the sensitivity and specificity were 90.02% and 58.78%,respectively.The AUC of miR-125b combined with HIF-1α for predicting allergic purpura was 0.910,and the sensitivity and specificity were 88.74% and 87.19%.Conclusion Serum miR-125b and HIF-1αexpression levels are increased in children with purpura,and they were negatively correlated with Th1/Th2 ratio.The miR-125b and HIF-1αexpression levels may be involved in disease development by regulating Th1/Th2 and mediating inflammation and are expected to be effective indicators for predicting the onset of children with purpura.