血清miR-144、miR-518b和ACR在早期诊断妊娠期高血压肾功能损害中的应用价值

Diagnostic value of the detection of serum miR-144,miR-518b and ACR in early diagnosis of renal impairment in patients with hypertensive disorder complicating pregnancy

目的研究血清miR-144,miR-518b和24 h尿蛋白定量与尿肌酐的比值(ACR)在早期诊断妊娠期高血压(HDCP)肾功能损害中的应用价值。方法选择2017至2018年就诊的HDCP患者118例,为HDCP组。根据病情不同分为妊娠高血压组(n=44),子痫前期轻度组(n=36)和子痫前期重度组(n=38)。选择同期体检的正常孕妇45例和健康体检女性30例为正常妊娠组和健康对照组。采用定量RT-PCR检测血清miR-144和miR-518b表达。比较各组血清miR-144,miR-518b,ACR和微量白蛋白(mAlb)水平,与HDCP严重程度,HDCP肾损害和肾损害严重程度的关系,及其在HDCP肾损伤中的诊断效能。结果HDCP组的miR-144表达明显低于正常妊娠组和健康对照组(P<0.01),而正常妊娠组明显低于健康对照组(P<0.01),随着HDCP病情严重程度的升高而降低,并随着肾功能损害分期升高而降低;HDCP组的miR-518b,ACR和mAlb水平明显高于正常妊娠组和健康对照组(P<0.01),而正常妊娠组明显高于健康对照组(P<0.01),随着HDCP病情严重程度的升高而升高,并随着肾功能损害分期升高而升高。肾功能异常组的血清miR-144表达明显低于肾功能正常组(P<0.01),而肾功能异常组血清miR-518b,ACR和mAlb水平明显高于肾功能正常组(P<0.01)。血清miR-144(Z=3.212,P<0.01),miR-518b(Z=2.332,P<0.05)和ACR(Z=2.722,P<0.01)在诊断HDCP肾功能损害具有较高的效能明显优于mALB,而miR-144,miR-518b和ACR指标之间差异无统计学意义(P>0.05)。联合检测(miR-144+miR-518b+ACR)的灵敏度为100%,特异性为86.1%,曲线下面积为0.980明显优于单个指标miR-144(Z=3.425,P<0.01),miR-518b(Z=3.817,P<0.01)和ACR(Z=3.592,P<0.01)指标。结论miR-144和miR-518b参与了HDCP肾损害的发生发展,血清miR-144、miR-518b和ACR检测在早期诊断HDCP肾功能损害具有较高的效能,联合检测优于单个指标。

Objective To investigate the diagnostic value of the detection of serum miR-144,miR-518b and 24h urine protein to urine creatinine ratio(ACR)in early diagnosis of renal impairment in patients with hypertensive disorder complicating pregnancy(HDCP).Methods A total of 118 patients with HDCP who were admitted and treated in our hospital from January 2017 to December 2018 were enrolled as HDCP group,moreover,according to the severity of disease,who were divided into gestational hypertension(n=44),mild preeclampsia group(n=36)and severe preeclampsia group(n=38).Menwhile the other 45 normal pregnant women and 30 healthy women were enrolled as normal pregnancy group and healthy control group.The serum levels of miR-144 and miR-518b were detected by quantitative RT-PCR.Moreover the serum levels of miR-144,miR-518b,ACR and microalbumin(mAlb)and the severity of HDCP were observed and compared among the groups.In addition the correlation between the severity of HDCP renal damage and the severity of renal damage,and their diagnostic efficacy in diagnosis of HDCP renal injury were investiagted.Results The expression levels of miR-144 in HDCP group was significantly lower than those in normal pregnancy group and healthy control group(P<0.01),however,which in normal pregnancy group were significantly lower than those in healthy control group(P<0.01),moreover,its levels were decreased with the severity of HDCP and renal function damage.Moreover the levels of miR-518b,ACR and mAlb in HDCP group were significantly higher than those in normal pregnancy group and healthy control group(P<0.01),however,which in normal pregnancy group were significantly higher than those in healthy control group(P<0.01),and their levels were increased with the severity of HDCP and renal function damage.In addition the serum levels of miR-144 in renal dysfunction group were significantly lower than those in normal renal function group(P<0.01),but,the serum levels of miR-518b,ACR and mAlb in renal dysfunction group were significantly higher than those in normal renal function group(P<0.01).The serum miR-144,miR-518b and ACR were superior to mALB in the diagnosis of HDCP renal dysfunction,however,there was no significant difference among miR-144,miR-518b and ACR(P>0.05).The sensitivity of combined detection(miR-144+miR-518b+ACR)was 100%,the specificity was 86.1%,and the area under the curve was 0.980,which was significantly better than that of miR-144,miR-518b and ACR(P<0.01).Conclusion The miR-144 and miR-518b are involved in the incidence and development of HDCP renal damage,and the detection of serum levels of miR-144,miR-518b and ACR has higher efficacy in early diagnosis of renal dysfunction due to HDCP,moreover,the combined detection is superior to single index detection.