重度子痫前期患者胎盘组织中缺氧适应相关基因的表达及其临床意义

Clinical significance of hypoxia inducible factor-prolyl hydroxylase 1 and factor inhibiting hypoxia inducible factor-1 expression in placentas of women with severe pre-eclampsia

目的探讨胎盘组织中缺氧诱导因子脯氨酸羟化酶1（HPH1）和因子抑制缺氧诱导因子1（FIH-1）在重度子痫前期发病和疾病进展中的作用。方法选择2006年7月至2007年7月在中国医科大学附属盛京医院妇产科住院选择剖宫产终止妊娠的重度子痫前期孕妇34例（重度子痫前期组）及正常晚期妊娠孕妇24例（对照组），采用RT—PCR和蛋白印迹法检测两组孕妇胎盘组织中的HPH1和FIH-1 mRNA及蛋白的表达，并与临床指标进行相关性分析。结果（1）重度子痫前期组孕妇胎盘组织中HPH1 mRNA及蛋白表达水平分别为0．40±0．04和59．5±3．4，显著低于对照组的0．84±0．12和71．6±1．7（P均〈0．01）；重度子痫前期组孕妇FIH-1 mRNA及蛋白表达水平分别为0．31±0．05和45．6±2．4，也显著低于对照组的0．43±0．04和54．9±2．1（P均〈0．01）。（2）重度子痫前期组孕妇胎盘组织中HPH1和FIH-1 mRNA及其蛋白表达水平与平均动脉压（MAP）均呈显著负相关关系，r均为-0．854（P均〈0．01）；与24h尿蛋白定量均呈显著负相关关系，r均为-0．936（P均〈0．01）；与有无眼底动脉痉挛均呈显著负相关关系，r均为-0．854（P均〈0．01）。（3）两组58例孕妇胎盘组织中的HPH1 mRNA表达水平高于FIH-1 mRNA的表达，分别为0．58±0．27和0．39±0．10，两者呈正相关关系，r为0．686（P〈0．01）；HPHI蛋白表达水平高于FIH-1蛋白的表达水平，分别为64．5±6．7和49．4±5．2，两者也呈正相关关系，r为0．947（P〈0．01）。结论HPH1和FIH-1的表达变化可能与重度子痫前期的发病及疾病进展相关。

Objective To investigate the role of hypoxia inducible factor （HIF）-prolyl hydroxylase 1 （HPH1） and factor inhibiting HIF-1 （ FIH-1 ） in placentas in the pathogenesis and development of severe pre-eclampsia. Methods RT-PCR and western blot analyses were used to detect the HPH1 and FIH-1 expression levels in placentas of 34 patients with severe pre-eclampsia and 24 cases of term pregnancy （normal pregnancy group） and their correlations with symptoms were analyzed. Results （1）The HPH1 mRNA and protein expression levels in placentas of severe pre-eclampsia group were 0.40 ±0. 04 and 59. 5 ±3.4 separately, significantly lower than those of normal pregnancy group, 0. 84 ±0. 12 and 71.6 ±1.7 （P 〈 0. 01 ）. The FIH-1 mRNA and protein expression levels in placentas of severe pre-eclampsia group were 0. 31 ±0. 05 and 45.6 ±2. 4 separately, significantly lower than those of normal pregnancy group, 0. 43 ±0. 04 and 54. 9 ±2. 1 （ P 〈 0. 01 ）. （2） The mRNA and protein expression levels of HPH1 and FIH-1 in severe pre-eclampsia group were all negatively correlated with mean arterial pressure （MAP） [ the Spearman correlation coefficient was - 0. 854 （ P 〈 0. 01 ） ], urinary protein per 24 hours [ the Spearman correlation coefficient was - 0. 936 （ P 〈 0. 01 ） ] and the occurrence of fundus oculi artery spasm [ the Spearman correlation coefficient was - 0. 854 （ P 〈 0. 01 ） ]. （3） The expression of HPH1 mRNA in placentas of all the 58 cases was 0. 58 ±0. 27, higher than the expression of FIH-1 mRNA, which was 0. 39±0. 10. There was a positive correlation between them. The pearson correlation coefficient was 0. 686 （ P 〈 0.01 ）. The expression of HPH1 protein in placentas of all the 58 cases was 64. 5 ±6. 7, higher than the expression of FIH-1, which was 49. 4 ± 5.2. There was a positive correlation between them. The Pearson correlation coefficient was 0. 947 （ P 〈 0. 01 ）. Conclusion The expression imbalance of HPHI and FIH-1 in placenta may play an important role in the pathogenesis and development of severe pre-eclampsia through inhibiting HIF-1α.