切换至 "中华医学电子期刊资源库"
高级检索
中华妇幼临床医学杂志(电子版)

中华妇幼临床医学杂志(电子版) ›› 2013, Vol. 09 ›› Issue (01) : 22 -26. doi: 10.3877/cma.j.issn.1673-5250.2013.01.006

所属专题： 文献；

论著

血管内皮生长因子及其受体与可溶性血管内皮生长因子受体-1对妊娠期糖尿病与围生儿结局的预测价值
汤栩文1, 谢晓斌2,*,*(), 林斯1   
  1. 1. 510623　广州，广州市妇女儿童医疗中心
    2. 广州医学院病理学教研室
  • 收稿日期:2012-11-05 修回日期:2013-01-09 出版日期:2013-02-01
  • 通信作者: 谢晓斌

Study of the Relationship Between Vascular Endothelial Growth Factor and Perinatal Outcome of Gestational Diabetes Mellitus

Xu-wen TANG1, Xiao-bin XIE2(), Si LIN1   

  1. 1. Guangzhou Women and Children's Medical Center, Guangzhou 510623, Guangdong Province, China
  • Received:2012-11-05 Revised:2013-01-09 Published:2013-02-01
  • Corresponding author: Xiao-bin XIE
  • About author:
    Corresponding author: XIE Xiao-bin, Email:
全文 ( ) 下载PDF ( ) 导出引用
引用本文：

汤栩文, 谢晓斌, 林斯. 血管内皮生长因子及其受体与可溶性血管内皮生长因子受体-1对妊娠期糖尿病与围生儿结局的预测价值[J/OL]. 中华妇幼临床医学杂志(电子版), 2013, 09(01): 22-26.

Xu-wen TANG, Xiao-bin XIE, Si LIN. Study of the Relationship Between Vascular Endothelial Growth Factor and Perinatal Outcome of Gestational Diabetes Mellitus[J/OL]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2013, 09(01): 22-26.

目的

探讨妊娠期糖尿病(GDM)孕妇血清中血管内皮生长因子(VEGF)及其受体(VEGFR)所介导的胎盘血管病变与围生儿结局间的关系，以及血清中可溶性血管内皮生长因子受体(sVEGFR)-1水平，对VEGF-VEGFR轴发挥的生物学效应。

方法

选取2011年1月至12月在本中心被诊断为GDM、孕龄为24～28孕周的孕妇100例纳入GDM组；选择同期在相同医院常规产前检查、相同孕龄的50例正常孕妇，纳入对照组。采集两组孕妇血样，测量糖化指标：空腹血糖(FPG)值，糖化血红蛋白(HbA1c)与VEGF。GDM组经常规干预治疗后，再采集血样测定FPG值，HbA1c及VEGF，并与对照组进行统计学分析。分娩后，收集胎盘，分析胎盘组织中VEGFR蛋白表达。根据GDM组孕妇分娩后的围生儿结局，将其分别纳入GDM围生儿异常组(n＝34)与GDM围生儿正常组(n＝66)(本研究遵循的程序符合本院人体试验委员会所制定的伦理学标准，得到该委员会批准，分组征得受试对象本人的知情同意，并与之签署临床研究知情同意书)。

结果

①GDM组孕妇血清VEGF水平、HbA1c及FPG值均明显高于对照组，差异有统计学意义(P<0.05)。②GDM组孕妇经干预治疗后，孕晚期FPG明显降低(P<0.05)，HbA1c与对照组比较，差异无统计学意义(P>0.05)，血清VEGF水平仍保持较高水平。③GDM组孕妇血清VEGF与sVEGFR-1水平呈负相关(r＝－0.497，P<0.01)。④与GDM组孕妇所分娩围生儿的血清VEGF水平显著高于对照组孕妇所分娩围生儿，且差异有统计学意义(P<0.05)。⑤采用多因素非条件logistic回归法对GDM组与对照组孕妇血清VEGF表达水平的分析结果显示，VEGF是GDM围生儿结局异常的危险因子(OR＝5.196, 95% CI: 1.845～14.610，P<0.001)。⑥采用Western印迹法测定胎盘组织中VEGFR蛋白表达量显示，GDM围生儿异常组较GDM围生儿正常组显著升高，差异有统计学意义(P<0.05)。

结论

①GDM孕妇血清VEGF升高是其围生儿结局的一个不利因素，血清VEGF水平高可作为GDM不良围生儿结局的预测指标。②血循环中sVEGFR-1可通过竞争结合方式中和VEGF，抑制其下游信号传递。血清低sVEGFR-1水平可作为GDM病变中VEGF-VEGFR轴过度活跃的生物标记。

关键词: 血管内皮生长因子, 可溶性血管内皮生长因子受体, 妊娠期糖尿病, 胎盘, 围生儿, 预测指标
Objective

To explore the relationship between serum vascular endothelial growth factor (VEGF) and its receptors for VEGF(VEGFR) levels in gestational diabetes mellitus (GDM) women and their perinatal outcomes, and biological effects of serum soluble receptors-1 for VEGF (sVEGFR-1) levels of VEGF-VEGFR axis played.

Methods

From January to December 2011, a total of 100 cases pregnant women diagnosed with GDM between 24-28 weeks gestational age were recruitment in this study as GDM group. Meanwhile recruitment of another 50 cases of normal pregnant women of corresponding gestational age as control group. Extracted blood samples of pregnant women in two groups, measure glycated index: Fasting plasma glucose(FPG), HbA1c, VEGF. After intervention treatment to GDM group, measured FPG, HbA1c, VEGF again and comparison to control group. Collected after delivery of placenta cryopreservation for analysis of tissue expression of VEGFR protein. And collection of maternals and infants clinical information.According perinatals outcome of GDM group, pregnant women were divided into perinatal outcome normal group(n=66) and perinatal outcome abnormal group(n=34). Informed consent was obtained from all participants.

Results

① GDM groups had higher serum VEGF levels, HbA1c and FPG compared with those of control group were much higher, too (P<0.05). ②FPG in GDM group in late pregnancy after intervention treatment. was significantly lower than that in control group(P<0.05). Level of HbA1c in GDM group and in control group had no significance difference (P>0.05). Level of serum VEGF remained high.③In GDM group, maternal serum VEGF and sVEGFR-1 levels were negatively correlated(r=-0.497, P<0.01). ④Serum VEGF level in perinatal outcome abnormal group had significantly higher than that in perinatal outcome normal group (P<0.05). ⑤ Multivariate unconditional logistic regression analysis showed that VEGF was a predictor of adverse perinatal outcome in GDM(OR=5.196, 95% CI: 1.845-14.610, P<0.001). ⑥Determined by Western blotting of VEGFR protein expression in the placenta was also much higher of pregnant women in perinatal outcome abnormal group than that in perinatal outcome normal group (P<0.05).

Conclusions

①High serum VEGF is negative factor for the GDM perinatal outcome. High levels of VEGF can be used as a GDM abnormal perinatal outcome predictor. ②sVEGFR-1 may be in the blood circulation by competitive binding VEGF. Inhibition of downstream signal transduction. Lower serum sVEGFR-1 levels could be as the GDM lesions of VEGF-VEGFR axis overactive biomarkers.

Key words: vascular endothelial growth factor, soluble receptors-1 for VEGF, gestation diabetes mellitus, placenta, perinatal, predictor
表1 两组孕妇血清VEGF，sVEGFR-1，HbA1c及FPG值比较(±s)
Table 1 Comparison of VEGF，sVEGFR-1，HbA1c and FPG between GDM group and control group at 28-32 gestational weeks (±s)
组别 n FPG(mmol/L) HbA1c (%) VEGF(pg/mL) sVEGFR-1(μg/L)
GDM组 100 6.27±0.88 6.45±1.26 211.17±27.19 16.23±1.57
对照组 50 4.81±0.72 5.68±0.52 94.35±21.18 29.36±2.14
t ? 2.87 2.61 13.34 10.42
P ? <0.05 <0.05 <0.01 <0.01
表2 GDM组孕妇经干预治疗后，血清VEGF，sVEGFR-1，HbA1c及FPG值与对照组比较(±s)
Table 2 Comparison of VEGF，sVEGFR-1，HbA1c and FPG between GDM group after treatment and control group(±s)
组别 n FPG(mmol/L) HbA1c (%) VEGF(pg/mL) sVEGFR-1(μg/L)
GDM组 100 5.69±0.74 5.71±0.92 204.27±28.38 18.56±1.61
对照组 50 4.70±0.69 5.47±0.53 91.50±20.42 28.15±1.95
t ? 1.76 1.85 12.84 9.13
P ? >0.05 >0.05 <0.01 <0.01
图1 胎盘组织中VEGFR蛋白的表达结果(1：对照组；2：GDM围生儿正常组；3：GDM围生儿异常组)
Figure 1 The expression of VEGFR protein in placental tissue(1: Control group; 2：Normal perinatal child of GDM; 3：Abnormal perinatal child of GDM)
[1]
Crowther CA, Hiller JE, Moss JR, et al. Effect of treatment of gestationaldiabetes mellitus on pregnancy outcomes[J]. N Engl J Med，2005，352(24):2477-2486.
[2]
Rowan JA. A trial in progress: Gestational diabetes. Treatment with metformin compared with insulin (the metformin in gestational diabetes [MiG] trial)[J]. Diabetes Care，2007，30 (Suppl 2):S214-219.
[3]
Gestational diabetes mellitus: NICE for the USA.Comparison of the American Diabete Association and the American College of Obstetricians and Gynecologists guidelines with the U．K. National Institute for health and clinical excellence guidelines[J]. Diabetes Care，2010，33(1):34-37.
[4]
Xu Y, Zhang YP, Liu XH.Incidence and associated factors of abnormal glucose metabolism[J/CD]．Chin J Obstet Gynecol Pediatr: Electron Ed, 2008，4(2):87-90.
[5]
Marini M, Vichi D, Toscano A, et al. Effect of impaired glucose tolerance during pregnancy on the expression of VEGF receptors in human placenta[J]. Reprod Fertil Dev，2008，20(7):789-801.
[6]
Salim MD, Al-Matubsi HY, El-Sharaky AS, et al. The levels of vascular endothelial growth factor-A and placental growth factor-2 in embryopathy associated with experimental diabetic gestation[J]. Growth Factor，2009，27(1):32-39.
[7]
Wathen KA, Sarvela J, Steenman F, et al. Changes in serum concentrations of soluble vascular endothelial growth factor receptor-1 after pregnancy[J]. Hum Reproduct, 2011，26(1):221-226.
[8]
Metzger BE, Lowe LP, Dyer AR, et al. Hyperglycemia and adverse pregnancy outcomes. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study Cooperative Research Group. N Engl J Med, 2008，358(19):1991-2002.
[9]
Chen Z, Yin YX, Xu JJ.Expression and significance of vascular endothelial growth factor and its receptor Fms-like tyrosine kinase-1 in placenta for patients with intrahepatic cholestasis of pregnancy[J/CD]. Chin J Obstet Gynecol Pediatr : Electron Ed, 2011，7(6):531-533.
[1] 李钱梅, 何冠南, 赵婧, 陈曦, 唐玉英, 马丽琼, 梁蓉, 袁桃, 李明星. 早孕期低危妊娠和高危妊娠胎盘微血流成像特征及预后分析[J/OL]. 中华医学超声杂志（电子版）, 2024, 21(07): 726-732.
[2] 何霞, 黄蓉, 祁文瑾. 胎膜早破孕妇胎盘与胎膜菌群丰度的高通量测序研究[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(05): 549-555.
[3] 韩肖燕, 杨桦. 中孕期孕妇血清胎盘生长因子水平低与胎儿不良预后的关系[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(04): 398-402.
[4] 邵小丽, 林燕, 张玲玲, 韩亚琴. 超声引导下子宫肌瘤注射聚桂醇硬化术联合术后米非司酮治疗临床疗效分析[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(03): 353-360.
[5] 黄福, 王黔, 金相任, 唐云川. VEGFR2、miR-27a-5p在胃癌组织中的表达与临床病理参数及预后的关系研究[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(05): 558-561.
[6] 朱佳琳, 方向, 贵诗雨, 黄丹, 周小雨, 郭文恺. 大鼠切口疝腹膜前间隙补片修补术后血清中VEGF 和Ang-1 的表达情况[J/OL]. 中华疝和腹壁外科杂志(电子版), 2024, 18(06): 703-707.
[7] 张敏龙, 杨翠平, 王博, 崔云杰, 金发光. MiR-200b-3p 通过抑制HIF-1α 表达减轻海水吸入诱导的肺水肿作用及机制[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(05): 696-700.
[8] 暴静, 吴霞, 田雅萍, 尹钢. 维生素D3联合孟鲁司特钠治疗支气管哮喘对血清VEGF、TGF-β1及肺功能的影响[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(01): 63-67.
[9] 庞丹, 孙刚, 伊乐, 丁立云, 钟美艳, 张杰, 于婷婷, 郭乐峰. 血清HIF-1α、VEGF、Flt-1的检测对ARDS的预后及临床意义[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(01): 127-130.
[10] 朱迎, 赵征, 许达, 陆录, 殷保兵. 免疫检查点抑制剂治疗肝细胞癌的进展与展望[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(01): 5-10.
[11] 洪凡, 陈敦金, 傅洋, 梁新月, 吴毅, 王晓怡. 体外受精-胚胎移植妊娠合并前置胎盘临床研究[J/OL]. 中华产科急救电子杂志, 2024, 13(03): 176-182.
[12] 胡淼, 杜丽丽, 张丽姿, 林琳, 张瑜亮, 古士锋, 古仲嘉, 赖思莹, 梁景英, 刘雨, 黄敏珊, 黄媛媛, 黄晴晴, 罗世君, 陈敦金. 体外受精/卵胞浆内单精子注射受孕患者胎盘植入分级及围产结局的研究[J/OL]. 中华产科急救电子杂志, 2024, 13(03): 183-189.
[13] 李婷, 滕银成. 体外受精-胚胎移植与前置胎盘[J/OL]. 中华产科急救电子杂志, 2024, 13(02): 84-87.
[14] 卫星, 孙路明. 辅助生殖技术与胎儿生长障碍[J/OL]. 中华产科急救电子杂志, 2024, 13(02): 88-92.
[15] 刘光华, 欧阳强, 俞炬明, 范国平, 欧敬民, 邱明科, 林霏开, 孙会贞, 张惠, 汪希鹏, 金敏菲. 双侧髂内动脉球囊阻断序贯子宫动脉栓塞辅助下剖宫产的临床应用[J/OL]. 中华介入放射学电子杂志, 2024, 12(01): 33-38.
阅读次数
全文


摘要

版权所有 中华医学会 中华医学电子音像出版社有限责任公司  京ICP备14006079号-1  网络出版服务许可证：(署)网出证(京)字第075号