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心脏丝氨酸蛋白酶及血管内皮因子在妊娠期高血压疾病中的表达及预测价值

发布时间:2019-04-29 16:23
【摘要】:目的:通过检测不同孕期孕妇血清中心脏丝氨酸蛋白酶(corin)、血管内皮生长因子(vascular endothelial growth factor,VEGF)、胎盘生长因子(placenta growth factor,PLGF)及可溶性血管内皮生长因子受体1(soluble vascular endothelial growth factor receptor 1,sFlt-1)水平,研究上述因子在妊娠期高血压疾病(hypertensive disorders complicating pregnancy,HDCP)患者及正常孕妇中的不同变化,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-2016年9月就诊于兰州大学第二医院产科门诊及住院的单胎妊娠孕妇,横断面研究孕早期、孕中期以及孕晚期孕妇血清中上述各因子水平,根据妊娠结局,将其分为HDCP组和正常妊娠对照组。其中筛选出HDCP患者孕早期(孕10~14周)血清标本24例为研究组,选取同时期健康孕妇孕早期血清标本24例作为正常对照组;筛选出HDCP患者孕中期(孕16~24周)血清标本55例为研究组,选取同时期健康孕妇孕中期血清标本55例作为正常对照组;选取HDCP患者孕晚期(孕28周之后)血清标本23例为研究组,并选取同时期健康孕妇孕晚期血清标本23例作为正常对照组。采用ELISA方法测定各组血清中corin、VEGF、PLGF、sFlt-1水平,应用统计学方法分析上述因子的组间差异,并应用Logistic回归及ROC曲线评价孕早中期各因子单独及联合检测在预测HDCP发生中的诊断价值。结果:1.孕早期,HDCP组与对照组比较,血清corin、VEGF及PLGF水平下降,两组比较均有统计学差异,P0.05;而血清sFlt-1水平、sFlt-1/PLGF比值升高,两组比较均有统计学差异,P0.05。2.孕中期,HDCP组与对照组比较,血清VEGF、PLGF水平下降,两组相比均有统计学差异,P0.05;而血清corin、sFlt-1水平及sFlt-1/PLGF比值升高,两组比较均有统计学差异,P0.05。3.孕晚期,HDCP组与对照组比较,血清VEGF、PLGF水平下降,两组比较均有统计学差异,P0.05;而血清corin、sFlt-1水平及sFlt-1/PLGF比值升高,两组比较均有统计学差异,P0.05。4.应用Logistic回归及ROC曲线评估孕早中期孕妇血清corin、VEGF、PLGF、sFlt-1及sFlt-1/PLGF比值,各血清因子对HDCP发生均有预测价值;且孕早期各因子联合预测概率PRE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比值的预测价值;孕中期各因子联合预测概率PRE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:1.孕早、中、晚期HDCP组与对照组比较孕妇血清corin、VEGF、PLGF、sFlt-1水平均有差异,说明上述各因子与HDCP的发生发展有关。2.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,而孕早、中期联合检测孕妇血清corin、VEGF、PLGF、sFlt-1水平对预测HDCP的发生与各单因子检测相比有更高的敏感性和特异性,结果更可靠,预测价值更高。
[Abstract]:Objective: to detect vascular endothelial growth factor (vascular endothelial growth factor,VEGF (corin),) and placental growth factor (placenta growth factor, (placenta growth factor,) in serum of pregnant women during different pregnancy. The levels of PLGF) and soluble vascular endothelial growth factor receptor 1 (soluble vascular endothelial growth factor receptor 1, sFlt 1) were measured in patients with hypertensive disorder complicating pregnancy (hypertensive disorders complicating pregnancy,HDCP) and normal pregnant women. The diagnostic value of the above factors in predicting the occurrence of HDCP in early and middle trimester of pregnancy was also discussed. Methods: single-child pregnant women were selected from December 2015 to September 2016 in the outpatient department and in-patient department of the second Hospital of Lanzhou University. The levels of above factors in the serum of pregnant women in early, middle and third trimester of pregnancy were studied on the basis of the outcome of pregnancy. They were divided into HDCP group and normal pregnancy control group. Among them, 24 serum samples of HDCP patients were selected as the study group, and 24 healthy pregnant women were selected as the normal control group during the same period of gestation, and 24 serum samples of the pregnant women were selected as the study group in the first trimester of pregnancy. 55 serum samples of HDCP patients in the second trimester of gestation (16 weeks of gestation) were selected as the study group, and 55 healthy pregnant women in the same period were selected as the normal control group. Serum samples from 23 patients with HDCP (after 28 weeks of gestation) were selected as the study group, and 23 serum samples from healthy pregnant women at the same period were selected as the normal control group. The levels of corin,VEGF,PLGF,sFlt-1 in serum of each group were measured by ELISA method, and the differences of the above factors between groups were analyzed by statistical method. Logistic regression and ROC curve were used to evaluate the diagnostic value of single and combined detection of each factor in the early and middle trimester of pregnancy in predicting the occurrence of HDCP. Results: 1. In the first trimester of pregnancy, the levels of serum corin,VEGF and PLGF in HDCP group were significantly lower than those in control group (P 0.05). The level of serum sFlt-1 and the ratio of sFlt-1/PLGF were significantly higher in the two groups than those in the control group (P 0.05.2). In the second trimester of gestation, the level of serum VEGF,PLGF in HDCP group was significantly lower than that in control group (P 0.05). The levels of serum corin,sFlt-1 and the ratio of sFlt-1/PLGF were significantly higher in the two groups than those in the control group (P0.05.3. 3.) In the third trimester of gestation, the level of serum VEGF,PLGF in HDCP group was lower than that in control group, and there was significant difference between the two groups (P 0.05). The levels of serum corin,sFlt-1 and the ratio of sFlt-1/PLGF were significantly higher in the two groups than those in the control group (P 0.05.4). Logistic regression and ROC curve were used to evaluate the ratio of serum corin,VEGF,PLGF,sFlt-1 and sFlt-1/PLGF in pregnant women in the early and middle trimester of pregnancy. All serum factors had predictive value for the occurrence of HDCP. In the first trimester of pregnancy, the area under the AUC of the combined prediction probability PRE was 0.851, and the maximum Joden index was 0.625. The corresponding sensitivity and specificity were 83.3% and 79.2%, respectively. It was obviously higher than the prediction value of the single detection index and the sFlt-1/PLGF ratio. In the second trimester of pregnancy, the area under the AUC of the combined prediction probability PRE was 0.927, the largest Yodden index was 0.691, the corresponding sensitivity and specificity were 87.3% and 82.8%, respectively, and the relative sensitivity and specificity were 87.3% and 82.8%, respectively. It was significantly higher than the single detection index and the predictive value of sFlt-1/PLGF. Conclusions: 1. The serum corin,VEGF,PLGF,sFlt-1 levels of pregnant women in the early, middle and late stages of HDCP were significantly different from those of the control group, indicating that the above factors were related to the occurrence and development of HDCP. 2. The detection of serum corin,VEGF,PLGF,sFlt-1 levels in pregnant women at early and middle stages is of predictive value to the occurrence of HDCP, while the combined detection of serum corin,VEGF,PLGF, in pregnant women at early and middle stages of pregnancy is of great value. The level of sFlt-1 has higher sensitivity and specificity in predicting the occurrence of HDCP than the single factor detection. The results are more reliable and the prediction value is higher.
【学位授予单位】:兰州大学
【学位级别】:硕士
【学位授予年份】:2017
【分类号】:R714.246

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