心脏丝氨酸蛋白酶及内皮生长因子与妊娠期高血压疾病的相关性及预测价值

Correlation and predictive value of Corin and endothelial growth factor in HDCP

目的研究不同孕期孕妇血清心脏丝氨酸蛋白酶(Corin)、血管内皮生长因子(VEGF)、胎盘生长因子(PLGF)及可溶性血管内皮生长因子受体1(sFlt-1)水平在妊娠期高血压疾病(HDCP)患者及正常孕妇中的不同变化,以及它们与HDCP发生发展的关系,并探讨孕早中期上述因子预测HDCP发生的诊断价值。方法选取2015年12月至2016年9月在兰州大学第二医院门诊产检及住院的单胎妊娠的孕妇,横断面研究孕早期、孕中期以及孕晚期孕妇,根据妊娠结局,将其分为HDCP组和正常妊娠对照组,选取孕早期48例(24例后期发展为HDCP)、孕中期110例(55例后期发展为HDCP)、孕晚期46例(23例为HDCP)孕妇,应用ELISA方法测定血清中Corin、VEGF、PLGF、sFlt-1水平,应用独立样本t检验的方法检测其差异性,并应用Logistic回归及ROC曲线评价孕早中期各因子单独及联合预测HDCP发生的价值。结果孕早、中、晚期HDCP组与正常妊娠对照组血清Corin、VEGF、PLGF、sFlt-1水平以及sFlt-1/PLGF值比较,差异均具有统计学意义(P<0.05);应用Logistic回归及ROC曲线法,发现在孕早中期Corin、VEGF、PLGF、sFlt-1及sFlt-1/PLGF各单项预测HDCP发生中均有一定的价值,然而把它们联合起来其预测价值明显更高,其中孕早期联合预测值预测概率的AUC下面积为0.851,约登指数最大为0.625,其对应的敏感度为83.3%,特异度为79.2%,明显高于各单项检测指标及sFlt-1/PLGF的预测价值;孕中期联合预测值预测概率的AUC下面积为0.927,约登指数最大为0.691,其对应的敏感度为87.3%,特异度为82.8%,明显高于各单项检测指标及sFlt-1/PLGF的预测价值。结论孕早中期检测孕妇血清Corin、VEGF、PLGF、sFlt-1水平对HDCP的发生有预测价值,而联合检测孕早中期Corin、VEGF、PLGF、sFlt-1对预测HDCP发生有更高的敏感度和特异度,结果更可靠,预测价值更高。

Objective The present project is to measure the maternal serum levels of Corin, vascular endothelial growth factor(VEGF), placenta growth factor(PLGF) and soluble vascular endothelial growth factor receptor 1(sFlt-1) in pregnant women with different gestational age, then to explore the changes of these factors in HDCP patients and normal pregnant women and their relationship with the development of HDCP. The aims of the study is to investigate the diagnostic value about hypertensive disorders complicating pregnancy(HDCP) of these factors in maternal serum in the early and middle trimester pregnancy. Methods There single pregnancy pregnant women were selected as study objects, who were received medical service in the Department of Gynecology and Obstetrics of Lanzhou University Second Hospital from December 2015 to September 2016. Detecting pregnant women with different trimesters pregnancy from the cross-sectional study. There pregnant women were divided into two groups according to the pregnancy outcome in every trimester pregnancy. In the first trimester, 48 cases of single pregnancy pregnant women were selected(including 24 cases who subsequently developed HDCP) and in the middle trimester, 110 cases of single pregnancy pregnant women were selected(including 55 cases who subsequently developed HDCP) and in the third trimester, 46 cases of single pregnancy pregnant women were selected(including 23 cases who were HDCP). The serum levels of Corin, VEGF, PLGF and sFlt-1 were measured by ELISA. The differences between the above factors were analyzed by statistical method. Logistic regression and ROC curve were used to evaluate the effects of different factors predicting the value of HDCP in the early and middle trimester pregnancy. Results In the all trimester pregnancy, the serum level of Corin, VEGF, PLGF, sFlt-1 and sFlt-1/PLGF value in the HDCP group were different with the normal pregnancy control group, the differences were statistically significant(P<0.05). The Logistic regression and ROC curve were used to evaluate the serum levels of Corin, VEGF, PLGF, sFlt-1 and sFlt-1/PLGF in the early and middle trimester pregnancy. The results showed that each individual had predictive value for HDCP. In the early trimester pregnancy, the area under curve of the combination predicted probability PRE was 0.851 and the Youden index was 0.625, and the corresponding sensitivity was 83.3% and the specificity was 79.2%, which was significantly higher than that of individual test index and sFlt-1/PLGF. In the middle trimester pregnancy, the area under curve of the combination predicted probability PRE was 0.927 and the Youden index was 0.691, and the corresponding sensitivity was 87.3% and the specificity was 82.8%, which was significantly higher than that of individual test index and sFlt-1/PLGF. Conclusions We find that there are predictable value for HDCP of the measurement the maternal serum levels of Corin, VEGF, PLGF and sFlt-1 in the early and middle trimester pregnancy. The combination of these factors have higher sensitivity and specificity, and the results are more reliable and with higher value.