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目的探讨缺氧诱导因子1α(HIF-1α)及其靶基因血管内皮细胞生长因子(VEGF)、可溶性血管内皮细胞生长因子受体1(sFlt-1)基因在子痫前期患者胎盘组织中的表达。方法采用免疫组化链霉菌抗生物素蛋白-过氧化物酶连接(SP)法对20例重度子痫前期患者(子痫前期组)和15例正常妊娠妇女(对照组)的胎盘组织中的HIF-1α、VEGF、sFlt-1蛋白表达进行检测；同时应用RT- PCR技术对两组孕妇胎盘组织中HIF-1α、VEGF、sFlt-1 mRNA水平进行检测,并进行相关性分析。结果(1)子痫前期组HIF-1α蛋白表达(+++)者9例(45%,9/20),sFlt-1蛋白表达(+++)者11例(55%,11/20),对照组分别为2例(13%,2/15)和3例(20%,3/15),两组分别比较,差异均有统计学意义(P＜0．05)；子痫前期组VEGF蛋白表达(+++)者3例(15%,3/20),明显低于对照组的7例(47%,7/15),两组比较,差异有统计学意义(P＜0．01)。(2)子痫前期组HIF-1αmRNA、sFlt-1 mRNA水平分别为0．604±0．013、0．898±0．041,对照组分别为0．208±0．007、0．559±0．244,两组分别比较,差异均有统计学意义(P＜0．05)；子痫前期组VEGF mRNA表达水平虽高于对照组,但差异无统计学意义(P＞0．05)。子痫前期组VEGF mRNA/sFlt-1 mRNA比值(0．439±0．009)低于对照组(0．824±0．011),两组比较,差异有统计学意义(P＜0．05)。(3)子痫前期组HIF-1αmRNA的表达与sFlt-1 mRNA表达呈正相关(r=0．577,P＜0．05),与VEGF mRNA/sFlt-1 mRNA比值呈负相关(r= -0．376,P＜0．05)。结论HIF-1α在子痫前期患者胎盘组织中表达水平明显升高,主要是通过调节VEGF、sFlt-1基因的转录,而影响滋养细胞的浸润和胎盘血管重铸,参与子痫前期的发病。
Objective To investigate the expression of hypoxia-inducible factor-1α (HIF-1α) and its target gene of vascular endothelial growth factor (VEGF) and soluble vascular endothelial growth factor receptor 1 (sFlt-1) in placenta of preeclampsia . Methods The placental tissues of 20 patients with severe preeclampsia (preeclampsia group) and 15 normal pregnant women (control group) were immunized with immunohistochemical streptavidin-peroxidase (SP) The expression of HIF-1α, VEGF and sFlt-1 were detected by RT-PCR. The levels of HIF-1α, VEGF and sFlt-1 mRNA in the placenta of the two groups were detected and their correlations were analyzed. Results (1) In the preeclampsia group, 9 cases (45%, 9/20) of HIF-1α protein expression (+++) and 11 cases (55%, 11/20) of sFlt-1 protein expression ) In the control group were 2 cases (13%, 2/15) and 3 cases (20%, 3/15) respectively. There were significant differences between the two groups (P <0.05) There were 3 cases (15%, 3/20) of VEGF protein expression in group (7 cases) and 7 cases (7 cases / 15 cases) in control group, the difference was statistically significant (P < 0.01). (2) The levels of HIF-1αmRNA and sFlt-1 mRNA in preeclampsia group were 0.604 ± 0.013 and 0.898 ± 0.041, respectively, while those in control group were 0.208 ± 0.007 and 0.559 ± 0.244, respectively. There was significant difference between the two groups (P <0.05). Although the expression of VEGF mRNA in preeclampsia group was higher than that in control group, the difference was not statistically significant (P> 0.05) . The ratio of VEGF mRNA / sFlt-1 mRNA in preeclampsia group (0.439 ± 0.009) was lower than that in control group (0.824 ± 0.011), the difference was statistically significant (P <0.05 ). (3) The expression of HIF-1αmRNA in preeclampsia group was positively correlated with the expression of sFlt-1 mRNA (r = 0.577, P <0.05), and negatively correlated with the ratio of VEGF mRNA / sFlt- 0.376, P <0.05). Conclusions The expression of HIF-1α in placenta of preeclampsia patients is obviously increased, mainly through regulating the transcription of VEGF and sFlt-1 gene, affecting the infiltration of trophoblast and placental vascular remodeling and participating in the pathogenesis of preeclampsia.