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可溶性 FMS 样酪氨酸激酶-1(sFlt-1)和血清胎盘生长因子(PlGF)作为异位妊娠和稽留流产的生物标志物。

Soluble FMS-like tyrosine kinase-1 (sFlt-1) and serum placental growth factor (PlGF) as biomarkers for ectopic pregnancy and missed abortion.

机构信息

Department of Obstetrics and Gynecology, University of Thessalia Medical School, Larissa 41222, Greece.

出版信息

J Clin Endocrinol Metab. 2011 Sep;96(9):E1444-51. doi: 10.1210/jc.2011-0037. Epub 2011 Jun 29.

DOI:10.1210/jc.2011-0037
PMID:21715541
Abstract

CONTEXT

Diagnosis of early pregnancy failure is hampered by the lack of reliable serological markers.

OBJECTIVE

We assessed whether a single serum measurement of placental growth factor (PlGF) and the soluble Flt-1 (sFlt-1) receptor of vascular endothelial growth factor at 6-8 wk gestation could differentiate failed pregnancies, whether ectopic pregnancies (EP) or missed abortions (MA), from healthy intrauterine pregnancies (IUP).

DESIGN AND SETTING

We conducted a prospective clinical study at a tertiary university hospital between January 2009 and February 2011.

PATIENTS

A total of 78 consecutive patients (38 EP, 40 MA) with failed early pregnancy and 50 IUP (control group) participated in the study.

INTERVENTION(S): Determination of serum PlGF and sFlt-1 has been carried out by ELISA. Gene expression of PlGF and Flt-1 in trophoblasts was performed by RT-PCR.

MAIN OUTCOME MEASURE(S): We investigated whether a single, combined serum measurement of the above markers could contribute to the differential diagnosis.

RESULTS

PlGF and sFlt-1 concentration was lower in both EP (mean, 14.60 ± 3.42/178.16 ± 76.03 pg/ml) and MA (mean, 16.25 ± 4.73/399.42 ± 337.54 pg/ml) compared to IUP (mean, 21.64 ± 5.68/1390.32 ± 655.37 pg/ml). sFlt-1 (P = 0.033) and sFlt-1/PlGF ratio (P = 0.029) but not PlGF had the ability to discriminate MA from EP. Compared to women with viable IUP, mRNA gene expression levels of PlGF and Flt-1 were considerably lower in women with MA and in women with EP.

CONCLUSIONS

Combined measurement of sFlt-1 and PlGF levels can differentiate normal from failed pregnancies, whereas sFlt-1 as well as sFlt-1/PlGF ratio can also discriminate EP from MA. PlGF and Flt-1 gene expression in trophoblasts from women with EP and MA appears impaired.

摘要

背景

早期妊娠失败的诊断受到缺乏可靠的血清标志物的阻碍。

目的

我们评估了在 6-8 周妊娠时单次测量胎盘生长因子(PlGF)和血管内皮生长因子可溶性 Flt-1(sFlt-1)受体是否可以区分异位妊娠(EP)或稽留流产(MA)与健康的宫内妊娠(IUP)。

设计和设置

我们在 2009 年 1 月至 2011 年 2 月期间在一家三级大学医院进行了一项前瞻性临床研究。

患者

78 例连续的早期妊娠失败患者(38 例 EP,40 例 MA)和 50 例 IUP(对照组)参与了这项研究。

干预措施

通过 ELISA 测定血清 PlGF 和 sFlt-1。通过 RT-PCR 检测滋养细胞中 PlGF 和 Flt-1 的基因表达。

主要观察指标

我们研究了单一、联合血清标志物测量是否有助于鉴别诊断。

结果

EP(平均值,14.60±3.42/178.16±76.03 pg/ml)和 MA(平均值,16.25±4.73/399.42±337.54 pg/ml)的 PlGF 和 sFlt-1 浓度均低于 IUP(平均值,21.64±5.68/1390.32±655.37 pg/ml)。sFlt-1(P=0.033)和 sFlt-1/PlGF 比值(P=0.029)而非 PlGF 能够区分 MA 与 EP。与有活力的 IUP 女性相比,MA 和 EP 女性的 PlGF 和 Flt-1 mRNA 基因表达水平明显降低。

结论

联合测量 sFlt-1 和 PlGF 水平可以区分正常妊娠和失败妊娠,而 sFlt-1 以及 sFlt-1/PlGF 比值也可以区分 EP 和 MA。EP 和 MA 患者的滋养细胞中 PlGF 和 Flt-1 基因表达似乎受损。

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