血清miR-124、miR-143水平与高血压性视网膜病变关系的研究

Relationships between levels of microRNA 124 and microRNA 143 in peripheral blood and hypertensive retinopathy

目的观察血清微小RNA-124(miR-124)、微小RNA-143(miR-143)在高血压性视网膜病变(HRP)患者中的变化及其临床意义。方法选取2017年3月-2019年6月中国核工业北京四○一医院眼科诊治HRP患者113例为研究对象(HRP组),并选择同期于医院健康体检者115例作为对照(健康对照组)。检测2组血压、血糖、血脂等相关指标,以及血清miR-124、miR-143及血管内皮生长因子(VEGF)、肿瘤坏死因子-α(TNF-α)、白介素-6(IL-6)水平;Pearson法分析HRP患者血清miR-124、miR-143与VEGF、TNF-α、IL-6水平的关系,Logistic回归分析HRP的危险因素;ROC曲线评价血清miR-124、miR-143表达水平对HRP的预测诊断价值。结果HRP组患者SBP、DBP、血清miR-143、VEGF、TNF-α、IL-6水平均明显高于健康对照组(t=17.842、23.082、13.812、23.099、6.808、13.508,P均<0.01),miR-124表达水平明显低于健康对照组(t=9.116,P<0.01)。血清miR-124表达水平与VEGF水平呈负相关(r=-0.404,P<0.01),血清miR-143表达水平与VEGF水平呈正相关(r=0.525,P<0.01)。SBP、DBP、VEGF、miR-143为HRP的危险因素[OR(95%CI)=1.425(1.136~1.788)、1.645(1.098~2.464)、1.501(1.043~2.159)、1.780(1.149~2.756),P均<0.001],miR-124是HRP的保护因素[OR(95%CI)=0.646(0.457~0.913),P<0.01]。血清中miR-124、miR-143对HRP预测诊断的ROC曲线下面积(AUC)分别为0.838、0.870,截断值分别为0.91、1.28,敏感度分别为84.1%、84.2%,特异度分别为71.3%、78.3%;两者联合诊断HRP的AUC为0.947,其敏感度、特异度分别为94.7%、82.7%。结论HRP患者血清中miR-124呈低表达,miR-143呈高表达,两者可能共同参与HRP的发生与发展,均为HRP发病的影响因素,两者联合可有效提高HRP的诊断价值。

Objective To observe the levels of microRNA 124(miR-124)and microRNA143(miR-143)in peripheral blood serum of patients with hypertensive retinopathy(HRP)and their clinical significances.Methods One hundred and thirteen patients with HRP who were admitted to our hospital from March 2017 to June 2019 were selected as the study subjects(HRP group),and 115 healthy persons who were examined in our hospital during the same period were selected for the control study(health group).The blood pressure,glycolipid and other related indicators were measured in the two groups,real-time fluorescence quantitative assay(qRT-PCR)was used to detect the levels of miR-124 and miR-143 in serum of the two groups,the levels of serum vascular endothelial growth factor(VEGF),tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were measured by enzyme-linked immunosorbent assay(ELISA),the relationships between levels of serum miR-124 and miR-143 and levels of VEGF,TNF-αand IL-6 in patients with HRP were analyzed,the influencing factors of HRP were analyzed,and the predictive diagnostic values of levels of serum miR-124 and miR-143 for HRP were evaluated.Results The systolic blood pressure,diastolic blood pressure,levels of serum miR-143,VEGF,TNF-αand IL-6 in HRP group were significantly higher than those in healthy group(t=17.842,t=23.082,t=13.812,t=23.099,t=6.808,t=13.508,P<0.001).The expression level of serum miR-124 in the HRP group was significantly lower than that in healthy group(t=9.116,P<0.001).There was a negative correlation between the level of serum miR-124 and the level of VEGF in patients with HRP(r=0.404,P<0.001).There was a positive correlation between the level of serum miR-143 and the level of VEGF(r=0.525,P<0.001).Systolic blood pressure,diastolic blood pressure,VEGF and miR-143 were risk factors for HRP[OR(95%CI)=1.425(1.136~1.788),1.645(1.098~2.464),1.501(1.043~2.159),1.780(1.149~2.756),P<0.001],and miR-124 was a protective factor for HRP[OR(95%CI)=0.646(0.457~0.913),P<0.001].The areas under the curve(AUC)of serum miR-124 and miR-143 for predicting the diagnostic value of HRP were 0.838 and 0.870,and the corresponding truncation values were 0.91 and 1.28,respectively.The corresponding sensitivities were 84.1%and 84.2%respectively,the specificities were 71.3%and 78.3%respectively.The AUC of the combined diagnosis of HRP was 0.947,and the sensitivity and specificity were 94.7%and 82.7%respectively.Conclusion The level of serum miR-124 is low and miR-143 is high in HRP patients.Both may be involved in the occurrence and development of HRP.Both are the influencing factors of the pathogenesis of HRP.The combination of them can effectively improve the diagnostic value of HRP.