缺氧诱导因子及其抑制因子在不同妊娠阶段绒毛及胎盘组织中的表达及意义

Expression of HIF-1α and its inhibitors in villi and placentas of different pregnant periods

目的探讨缺氧诱导因子-1α(HIF-1α)及其抑制因子——PHD1、PHD2和因子抑制低氧诱导因子-1(FIH-1)在不同妊娠阶段绒毛和胎盘组织中的表达及意义。方法 2007年1月至2007年7月在中国医科大学附属盛京医院,采用免疫组化方法检测14例10周以内早孕者、11例10～12周早孕者、8例中孕者及24例正常晚期妊娠者绒毛和胎盘组织中的HIF-1α、PHD1、PHD2和FIH-1基因的蛋白水平。对四组的表达水平进行比较分析。结果 (1)HIF-1α、PHD1、PHD2和FIH-1基因的蛋白均主要表达在合体滋养细胞和细胞滋养细胞的胞浆中。(2)HIF-1α、PHD1、PHD2和FIH-1在10周以内早孕组(强阳性率分别为50.00%、0、28.57%及0)、10～12周早孕组(强阳性率分别为0、81.82%、0及90.91%)、中孕组(强阳性率分别为0、37.50%、0及25.00%)及正常晚孕组(强阳性率分别为8.33%、29.17%、8.33%及54.17%)中表达差异均有统计学意义(P<0.001;P<0.001;P=0.002;P<0.001)。其中HIF-1α和PHD2均在10周以内的早孕期表达最强,10～12周早孕期显著下降,中孕期有所升高,至晚孕期进一步升高。PHD1和FIH-1与之相反,均在10周以内的早孕期表达最低,10～12周早孕期显著增强,此后在中孕期有所下降,至晚孕期进一步下降。结论 PHD1、2和FIH-1可能在妊娠进展过程中通过调节HIF-1α参与对滋养细胞浸润的调控和胎盘发育,对于妊娠成功起重要调节作用。

Objective To investigate the different expression and physiological signification of HIF-1α, PHD1 ,PHD2 and FIH-I in the villi and placentas of different pregnant periods. Methods Immunohistochemical assay was used to detect the HIF-1α, PHD1 ,PHD2 and FIH-1 protein expression levels in villi of 14 early pregnant women in 10 weeks and 11 early pregnant women in 10 - 12 weeks; and in placenta of 8 second trimester pregnant women and 24 normal late pregnant women. Results （ 1 ） The HIF-1α, PHD1, PHD2 and FIH-1 protein was all mainly distributed in the cytoplasm of syncytiotrophoblast and cytotrophoblast in the four classes. （2） There was significantly difference in the four classes （P 〈 0. 001 ;P 〈 0. 001 ; P = 0. 002 ; P 〈 0. 001 ）. The most strong expression of HIF-1 α and PHD2 was observed in the villi of early pregnant women in 10 weeks, and significantly decreased in the villi of the early pregnant women in 10 - 12 weeks, and slightly increased in the palcenta of the second trimester pregnant women, and more increased in the placenta of late pregnant women but still lower than early pregnancy in 10 weeks. The expression of PHD1 and FIH-lwas the lowest in the villi of the pregnant women in 10 weeks, and significantly increased in the villi of the pregnant women in 10 - 12 weeks, and then slightly decreased in the palcenta of the second trimester pregnant women, and more decreased in the placenta of late pregnant women but still higher than early pregnancy in 10 weeks. Conclusion There was difference in the expres- sion of protein of HIF-1α ,PHD1 ,PHD2 and FIH-1 in the villi and placentas of different pregnant periods. PHD1, PHD2 and FIH-1 might play an important regulated role in the process of pregnancy through regulation to HIF-1α.