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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 changes of soluble vascular endothelial growth factor receptor 1 (sFlt-1) in the placenta of preeclampsia and its significance. Methods (1) 30 cases of preeclampsia (preeclampsia group, 11 cases of mild preeclampsia and 19 cases of severe preeclampsia) and 45 healthy pregnant women (control group) were detected by immunohistochemistry and RT- Group, including 18 cases of early pregnancy, 12 cases of middle-term pregnancy, 15 cases of late pregnancy) placenta tissue protein and sFlt-1 expression levels. (2) The serum levels of vascular endothelial growth factor (VEGF) and sFlt-1 in each group were determined by enzyme-linked immunosorbent assay (ELISA). Results (1) The expression level of sFlt-1 mRNA in placenta of preeclampsia group was 0.90 ± 0.11 and that in the control group was 0.80 ± 0.06, the difference was statistically significant ( P <0.01). Preeclampsia severe patients was 0.93 ± 0.12, mild preeclampsia patients was 0.85 ± 0.05, the difference between the two groups was also statistically significant (P <0.05). (2) The expression level of sFlt-1 protein in placenta of preeclampsia group was 0.156 ± 0.008, while that in control group was 0.143 ± 0.009, there was statistically significant difference between the two groups (P <0.01). The expression of sFlt-1 protein in severe preeclampsia group was 0.159 ± 0.008, and mild preeclampsia group was 0.151 ± 0.005 , The difference was also statistically significant (P <0.05). (3) The serum levels of VEGF and sFlt-1 in pregnant women with preeclampsia were (19.3 ± 2.9) ng / L and (30.2 ± 13.7) μg / L, respectively. The pregnant women in the control group were ( 30.2 ± 3.1) ng / L and (7.4 ± 3.1) μg / L, respectively. The difference was statistically significant (P <0.01). (4) There was a positive correlation between serum sFlt-1 level and placental sFlt-1 protein and mRNA expression in the control group (r = 0.439, P <0.01; r = 0.314, P <0.05). Serum sFlt-1 levels in pregnant women with preeclampsia were also positively correlated with placental sFlt-1 protein and mRNA levels (r = 0.383, r = 0.372; P <0.05). Conclusion The up-regulation of sFlt-1 mRNA expression and the overexpression of sFlt-1 protein in placenta of preeclampsia may result in the increase of circulating sFlt-1 level, which may be involved in the pathophysiological process of preeclampsia.