摘要
目的探讨缺氧诱导因子1α（HIF-1α）和血管内皮生长因子（VEGF）在妊娠期糖尿病（GDM）胎盘组织中的表达及其与胎盘组织形态学异常和妊娠结局的关系。方法选取2010年10月至2011年10月在青岛大学医学院附属医院住院的GDM患者44例，按空腹血糖是否≥5．8mmol／L分为血糖控制欠佳组（A组）10例和良好组（B组）34例，以同期健康孕妇37名为对照组（C组）。采用苏木精伊红（HE）染色法检测胎盘病理形态学，免疫组化和逆转录聚合酶链反应（RT-PCR）技术测定HIF-1α和VEGFmRNA及蛋白在胎盘中的表达，并比较各组差别与妊娠结局关系。与胎盘组织HIF-1α、VEGF相关因素采用Pearson单因素相关分析，P〈0．05为差异有统计学意义。结果（1）A组出现妊娠期高血压、产后出血、羊水过多、早产儿、巨大儿、新生儿低血糖等例数明显高于其他两组；（2）GDM组（A＋B）患者绒毛成熟不良、干绒毛小动脉增厚和胎盘绒毛间质毛细血管充盈的发生比例[61．4％（27／44）、38．6％（17／44）、50．0％（22／44）]与C组[13．5％（5／37）、10．8％（4／37）、18．9％（7／37）]比较差异有统计学意义（X^2值分别为19．260、8．100、8．450，均P〈0．05）；（3）A、B、C3组患者胎盘HIF-1αmRNA表达水平分别为0．91±0．13、0．72±0．12、0．47±0．11；VEGF mRNA表达为0．96±0．23、0．75±0．27、0．43±0．14，差异有统计学意义（F=67．300、33．250，均P〈0．05）；（4）A、B、C3组患者胎盘HIF-1α蛋白阳性表达率分别为90．0％、82．4％、32．4％；VEGF蛋白阳性表达率分别为100％、88．2％、35．1％，差异有统计学意义（X^2=22．632、28．115，均P〈0．05）；（5）胎盘组织HIF-1α和VEGF蛋白与绒毛成熟不良（r=0．764、0．875）、干绒毛小动脉增厚（r=0．655、0．885）及毛细血管充盈（r=0．685、0．766）呈正相关（均P〈0．05）。结论GDM患者血糖控制状态与胎盘组织中HIF-1α和VEGFmRNA和蛋白高表达有关，可能导致胎盘组织病理形态学的异常，对妊娠结局产生不良影响。
Objective To investigate the expression of placental hypoxia-inducible factor-1α （HIF-1α） and vascular epithelial growth factor （VEGF） in gestational diabetes mellitus （GDM） and its correlation with placental histological abnormalities and GDM pregnancy outcomes. Methods A case-control study was performed in 44 women with GDM, including 10 cases with not well-controlled glucose level （group A） and 34 cases with well-controlled glucose level （group B ）, and 37 healthy pregnant women （group C） with 36 -41 pregnancy weeks and delivered between October 2010 to October 2011 Placental tissue was histologically examined by HE staining method. The protein expression of HIF-1α and VEGF in placenta was detected by immunohistoehemistry. The expression of HIF-1αand VEGF mRNA in placenta was detected by RT-PCR,to compare the differential expression of HIF-1α and VEGF between three groups, and its relationship with pregnancy outcomes. Data was compared using Pearson correlation. P values 〈 0. 05 were considered statistically significant. Results （1） Women in group A were more likely to develop gestational hypertension, postpartum hemorrhage, polyhydramnios, premature delivery, macrosomia delivery and neonatal hypoglycemia delivery than other groups （ P 〈 0. 05 ）. （2） The presence of villous immaturity,vascular thickening and intervillous capillary enlargement was significantly increased in the placenta of GDM （P 〈0. 05）. （3） The expression of HIF-1α and VEGF mRNA in group A （0. 91±0. 13 and 0. 96 ±0. 23, respectively） and B （0.72 ± 0.12 and 0. 75±0. 27, respectively ） was significantly more thaa which, in group C （0.47±0. 11 and 0.43 ±0. 14, respectively, P〈0.05）. （4） The protein of HIF-1α and VEGF was expressed in all groups. The protein expression of HIF-1α and VEGF in group A （90. 0% and 100% , respectively） and group B （82.4% and 88.2% , respectively） was significantly more than which in group C （32. 4% and 35.1%, respectively, P 〈0. 05）. （5） The protein expression of HIF-1α and VEGF in GDM groups was positively correlated with the presence of villous immaturity （ r = 0. 764, 0. 875, respectively, P 〈 0. 05 ）, stem villus arteriole thickening （ r = 0. 655, 0. 885, respectively, P 〈 0. 05 ） and intervillous capillary congestion （r = 0. 685,0. 766, respectively, P 〈 0. 05）. Conclusions Over-expression of HIF-1α and VEGF in GDM placenta may be related to the placenta angiogenesis and maturation abnormalities, which is associated with adverse pregnancy outcomes of GDM.
出处
《中华糖尿病杂志》
CAS
CSCD
2013年第5期287-292,共6页
CHINESE JOURNAL OF DIABETES MELLITUS
基金
青岛市科技局资助课题（Kzd-12）
关键词
妊娠期糖尿病
胎盘
缺氧诱导因子1Α
血管内皮生长因子
Gestational diabetes mellitus
Placenta
Hypoxia-inducible factor-1α
Vascularepithelial growth factor
