探讨妊娠期高血压患者血清微小RNA(miRNA)-210、-204-5p、-376c与其血液流变学指标的相关性，以及其诊断价值。

采用简单随机抽样方法，随机抽取2016年10月至2018年10月，于河北省黄骅市人民医院收治的妊娠期高血压患者80例为研究对象，并纳入研究组(n＝80)。采用相同抽样方法，随机抽取同期于本院接受定期产前检查的80例中孕期正常妊娠妇女为对照，纳入对照组(n＝80)。采用实时荧光定量PCR，检测2组受试者血清miRNA-210、-204-5p及-376c的相对表达量。采用全自动血细胞分析仪，检测2组受试者的血液流变学指标。2组受试者血清miRNA-210、-204-5p、-376c相对表达量及血液流变学指标比较，采用成组t检验。采用受试者工作曲线下面积(ROC-AUC)，分析血清miRNA-210、-204-5p及-376c的相对表达量，对妊娠期高血压的诊断价值。采用Pearson相关系数分析妊娠期高血压患者血清miRNA-210、-204-5p及-376c的相对表达量与其血液流变学指标的相关性。本研究获得河北省黄骅市人民医院伦理委员会批准(批准文号：18101523)，并且受试者均签署临床研究知情同意书。2组受试者的年龄、入组时孕龄、孕前人体质量指数、孕次、产次等一般临床资料分别比较，差异均无统计学意义(P>0.05)。

①研究组患者血清miRNA-210、-204-5p的相对表达量分别为(1.56±0.35)与(1.78±0.40)，均显著高于对照组的(0.59±0.11)与(0.72±0.15)，研究组患者血清miRNA-376c的相对表达量为(0.33±0.09)，却显著低于对照组的(1.24±0.32)，2组上述指标分别比较，差异均有统计学意义(t＝23.648、22.193、24.485，均为P<0.001)。②血清miRNA-210、-204-5p及-376c的相对表达量诊断妊娠期高血压的ROC-AUC分别为0.824(95%CI：0.738～0.902，P<0.001)，0.871(95%CI：0.810～0.943，P<0.001)，0.833(95%CI：0.746～0.908，P<0.001)。根据约登指数最大原则，血清miRNA-210、-204-5p及-376c的相对表达量，对于诊断妊娠期高血压的最佳临界值分别为0.696、1.512及0.712，此时其诊断妊娠期高血压的敏感度分别为83.3%、93.1%及85.0%，特异度分别为85.0%、75.0%及85.0%。③研究组患者的全血低切黏度(WRV)、低切还原黏度(LSRV)、血浆黏度(PV)分别为(7.9±1.5) mPa·s、(17.6±3.6) mPa·s、(1.6±0.3) mPa·s，分别显著高于对照组的(7.2±1.3) mPa·s、(15.6±3.4) mPa·s、(1.2±0.2) mPa·s，2组上述指标比较，差异均有统计学意义(t＝3.154、P＝0.002，t＝3.613、P<0.001，t＝9.923、P<0.001)。④妊娠期高血压患者血清miRNA-210相对表达量与其WRV、LSRV、PV，均呈正相关关系(r＝0.343、P＝0.002，r＝0.415、P<0.001，r＝0.287，P＝0.001)；血清miRNA-204-5p相对表达量与PV亦呈正相关关系(r＝0.326、P＝0.003)；miRNA-376c相对表达量与WRV、LSRV，均呈正相关关系(r＝0.317、P＝0.004，r＝0.351、P＝0.001)。

妊娠期高血压患者血清miRNA-210、-204-5p、-376c相对表达量与其血液流变学指标存在相关性，并且有望成为诊断妊娠期高血压的潜在生物标志物。

To investigate correlations between serum microRNA (miRNA)-210, -204-5p, -376c and hemorheology indexes in patients with pregnancy-induced hypertension and their diagnostic values.

Eighty patients with pregnancy-induced hypertension admitted in Huanghua Municipal People′s Hospital of Hebei Province from October 2016 to October 2018 were randomly selected as research subjects by simple random sampling method and enrolled into study group (n=80). And 80 normal pregnant women in the second trimester were randomly selected by the same method during the same period in the same hospital as control group (n=80). Real-time quantitative PCR was used to detect relative expression levels of serum miRNA-210, -204-5p, -376 of two groups. Hemorheology indexes were measured in two groups of subjects by automatic blood cell analyzer. Independent-samples t test was used to compare the relative expression levels of serum miRNA-210, -204-5p, -376 and hemorheology indexes between two groups. Area under receiver operating characteristic curve (ROC-AUC) was used to analyze the diagnostic values of relative expression levels of serum miRNA-210, -204-5p, -376 in diagnosis of pregnancy-induced hypertension. Pearson correlation coefficient was used to analyze the correlation between expression levels of serum miRNA-210, -204-5p and -376c and hemorheology indexes in patients with pregnancy-induced hypertension. This study was approved by the Ethics Committee of Huanghua Municipal People′s Hospital of Hebei Province (Approval No. 18101523). Clinical research informed consent was obtained from each participate. There were no statistical differences in the general clinical data such as age, gestational age at the time of enrollment, body mass index before pregnancy, gravidity, parity of patients, and so on (P>0.05).

①The relative expression levels of serum miRNA-210 and miRNA-204-5p in study group were (1.56±0.35) and (1.78±0.40), respectively, which were higher than those (0.59±0.11), (0.72±0.15) in control group, respectively, and relative expression level of serum miRNA-376c in study group was (0.33±0.09), which was lower than that (1.24±0.32) in control group, and all the differences between two groups were statistically different (t=23.648, 22.193, 24.485; all P<0.001). ②The ROC-AUC of relative expression levels of serum miRNA-210, -204-5p, and -376c in diagnosis of pregnancy-induced hypertension were 0.824 (95%CI: 0.738-0.902, P<0.001), 0.871 (95%CI: 0.810-0.943, P<0.001), 0.833 (95%CI: 0.746-0.908, P<0.001), respectively. According to the maximum principle of Youden index, the optimal cut-off values of relative expression levels of serum miRNA-210, -204-5p, and -376c in diagnosis of pregnancy-induced hypertension were 0.696, 1.512, and 0.712, respectively. And the sensitivities for diagnosis of pregnancy-induced hypertension were 83.3%, 93.1% and 85.0%, respectively, and the specificities were 85.0%, 75.0% and 85.0%, respectively. ③The wholeblood reduced viscosity (WRV), low shear reduction viscosity (LSRV) and plasma viscosity (PV) of patients with pregnancy-induced hypertension in study group were (7.9±1.5) mPa·s, (17.6±3.6) mPa·s, (1.6±0.3) mPa·s, respectively, which were higher than those (7.2±1.3) mPa·s, (15.6±3.4) mPa·s, (1.2±0.2) mPa·s of healthy pregnant women in control group, respectively, and all the differences were statistically significant (t=3.154, P=0.002; t=3.613, P<0.001; t=9.923, P<0.001). ④There was a positive correlation between relative expression levels of serum miRNA-210 and WRV, LSRV and PV, respectively (r=0.343, P=0.002; r=0.415, P<0.001; r=0.287, P=0.001). There was a positive correlation between relative expression levels of serum miRNA-204-5p and PV (r=0.326, P=0.003). There was a positive correlation between relative expression levels of serum miRNA-376c and WRV, LSRV, respectively (r=0.317, P=0.004; r=0.351, P=0.001).

Relative expression levels of serum miRNA-210, miRNA-204-5p and miRNA-376c are associated with hemorheology indexes, and can be used as potential biomarkers for the diagnosis of pregnancy-induced hypertension, perhaps.