可溶性血管内皮生长因子受体1在子痫前期患者胎盘组织中的表达及意义

Expression and significance of soluble fms-like tyrosine kinase 1 in preeclampsia placenta

目的探讨可溶性血管内皮生长因子受体1(sFlt-1)在子痫前期患者胎盘组织中的mRNA及蛋白表达水平变化及其意义。方法(1)采用免疫组化方法及RT-PCR技术分别检测30例子痫前期患者(子痫前期组,其中轻度子痫前期11例,重度子痫前期19例)及45例健康孕妇(对照组,其中早期妊娠18例、中期妊娠12例、晚期妊娠15例)胎盘组织中sFlt-1的蛋白及mRNA表达水平。(2)采用酶联免疫吸附试验(ELISA)测定各组孕妇血清中血管内皮生长因子(VEGF)及sFlt-1水平。结果(1)子痫前期组胎盘组织中sFlt-1 mRNA表达水平为0．90±0．11,对照组晚期妊娠妇女为0．80±0．06,两者比较,差异有统计学意义(P<0．01)。子痫前期组重度患者为0．93±0．12,子痫前期组轻度患者为0．85±0．05,两者比较,差异也有统计学意义(P<0．05)。(2)sFlt-1蛋白在子痫前期组患者胎盘组织中的表达水平为0．156±0．008,对照组中晚期妊娠妇女为0．143±0．009,两者比较,差异有统计学意义(P<0．01);子痫前期组重度患者sFlt-1蛋白表达水平为0．159±0．008,子痫前期组轻度患者为0．151±0．005,两者比较,差异也有统计学意义(P<0．05)。(3)子痫前期组孕妇血清VEGF、sFlt-1水平分别为(19．3±2．9)ng／L、(30．2±13．7)μg／L,对照组晚期妊娠妇女为(30．2±3．1)ng／L、(7．4±3．1)μg／L,两者比较,差异有统计学意义(P<0．01)。(4)对照组孕妇血清sFlt-1水平与胎盘sFlt-1蛋白及mRNA表达水平呈正相关关系(r=0．439,P<0．01;r=0．314,P< 0．05);子痫前期组孕妇血清sFlt-1水平与胎盘sFlt-1蛋白及mRNA表达水平也呈正相关关系(r= 0．383,r=0．372;P均<0．05)。结论子痫前期患者胎盘组织中sFlt-1 mRNA表达水平上调及sFlt-1蛋白过度表达,可引起循环中sFlt-1水平升高,从而参与子痫前期的病理生理过程。

Objective To investigate the expression and significance of serum soluble fms-like tyrosine kinase 1 （sFlt-1） in preeclampsia placenta. Methods Immunohistochemistry and semiquantitative RT-PCR were used to investigate the expression of sFlt-1 and sFlt-1 mRNA in placenta of 30 women with preeclampsia（ including mild and moderate preeclampsia 11 cases, severe preeclampsia 19 cases） and 45 normal pregnant women （ including first trimester pregnancy 18 cases, 2nd trimester pregnancy 12 cases, and 3rd trimester pregnancy 15 cases）. The levels of vascular endothelial growth factor（VEGF） and sFlt-1 in serum were detected by enzyme linked immunosorbent assay. Results （ 1 ） The expression of sFlt-1 mRNA was significantly higher in preeclampsia group（0. 90 ＋ 0. 11 ） compared with the third trimester group （0. 80 ＋0. 06;P 〈0. 01 ） , and was higher in the severe preeclampsia group（0. 93 ＋0. 12） than that in the mild group （ 0. 85 ＋ 0. 05 ; P 〈 0. 05 ） . （ 2 ） The mean density of sFlt-1 in preeclampsia placenta （0. 156 ±0. 008） was significantly higher than that in the third trimester group（0.143 ±0. 009 ,P 〈0. 01 ）, and was higher in the severe group（0. 159 ±0.008） than in the mild group（0. 151 ±0.005;P 〈0.05）. （ 3 ） The level of VEGF in serum of the preeclampsia group （ 19. 3 ± 2.9 ） ng/L was significantly lower than that of the third trimester group [（30.2 ± 3.1） ng/L,P 〈0.01].The level of sFlt-1 in serum of the preeclampsia group （ 30. 2 ± 13.7 ） μg/L was significantly higher than that of the third trimester group [ （7.4 ± 3. 1 ） μg/L,P 〈 0. 01 ]. （4） There was significant correlation between the serum level of sFlt-1 and the expression of sFlt-1 mRNA or sFlt-1 in placenta of normal pregnancy group （ r = 0. 314, P 〈 0. 05 ; r = 0.439,P〈0.01） andpreeclampsiagroups（r=0.372, r=0.383; P〈0.05）. Condusion Upregulation of sFlt-1 mRNA and excess expression of sFlt-1 in placenta may induce higher level of sFh-1 in serum, which may be involved in the pathophysiological processes of preeclampsia.