胎盘中血管内皮生长因子及其受体1改变与子痫前期的相关性研究

Correlation between the changes of placental vascular endothelial growth factor and receptor 1 and preeclampsia

目的探讨胎盘中血管内皮生长因子(VEGF)及其可溶性受体1(s Flt-1)的变化与妊娠期高血压疾病的关系。方法采用半定量逆转录PCR法和免疫组织化学染色法检测20例正常人工流产绒毛组织、40例正常妊娠晚期、40例轻度子痫前期及40例重度子痫前期孕妇胎盘组织中VEGF及s Flt-1的表达及胎盘微血管密度(MVD)。结果子痫前期和正常妊娠孕妇绒毛或胎盘中均有VEGF、s Flt-1 mRNA和蛋白的表达。正常妊娠早期组、正常妊娠晚期组、轻度子痫前期组及重度子痫前期组VEGF、s Flt mRNA及蛋白表达水平两两比较差异均具有统计学意义(P均<0.01)。随着妊娠的进展,胎盘MVD逐渐增加,而在子痫前期孕妇中逐渐减少,组间两两比较差异均有统计学意义(P均<0.01)。轻、中度子痫前期胎盘组织中VEGF与s Flt-1 mRNA和蛋白表达水平均呈负相关(P均<0.05)。各组绒毛或胎盘组织中MVD与VEGF mRNA和蛋白表达水平均呈正相关(P均<0.05),而与s Flt-1 mRNA和蛋白质表达呈负相关(P均<0.05)。结论 VEGF和s Flt-1参与妊娠期高血压疾病的发生、发展,VEGF和s Flt-1在妊娠期高血压疾病的发病过程中可能存在着相反的关系,也就是VEGF对妊娠期高血压疾病的发生具有保护作用而s Flt-1则对其具有促进作用。

Objective To investigate the relationship between the alterations in placental vascular endothelial growth factor（ VEGF） and soluble receptor 1（ sFlt-1） and hypertension during gestation period.Methods The expression of VEGF and sFlt-1 and microvascular density（ MVD） in the villi of twenty healthy women with normal induced abortion and the placental tissues of 40 with late pregnancy,40 with mild preeclampsia and 40 with severe preeclampsia were measured using semi-quantitative reverse transcription PCR and immunohistochemical staining. Results At both protein and mRNA levels,VEGF and sFlt-1 were expressed in the villi or placenta from healthy pregnant women and those with preeclampsia. The expression of VEGF and s Flt at both protein and mRNA levels significantly differed between any two groups among early and late pregnancy,mild and severe preeclampsia groups（ all P〈0. 01）. Along with the development of pregnancy,the placental MVD was gradually increased,whereas steadily decreased in pregnant women with preeclampsia with statistical significance between any two groups（ all P〈0. 01）. In the mild and moderate preeclampsia groups,the expression of placental VEGF mRNA and protein was negatively correlated with those of sFlt-1（ all P〈0. 05）. In each group,MVD was positively correlated with expression of VEGF mRNA and protein（ all P〈0. 05）. However,MVD was negatively correlated with the expression of sFlt-1mRNA and protein（ all P〈0. 05）. Conclusions VEGF and sFlt-1 participate in the incidence and progression of hypertension during gestation period. These two factors probably play different roles in the process. VEGF is help to prevent the incidence of gestational hypertension,whereas sFlt-1 exerts a promoting effect.