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

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。

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

OBJECTIVE: To investigate the expression and significance of serum soluble fms-like tyrosine kinase 1 (sFlt-1) in preeclampsia placenta. METHODS: Immunohistochemistry and semi-quantitative 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) microg/L was significantly higher than that of the third trimester group [(7.4 +/- 3.1) microg/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) and preeclampsia groups (r = 0.372, r = 0.383; P < 0.05). CONCLUSION: Upregulation of sFlt-1mRNA and excess expression of sFlt-1 in placenta may induce higher level of sFlt-1 in serum, which may be involved in the pathophysiological processes of preeclampsia.