缺氧诱导因子-1α及其靶基因在双胎输血综合征胎盘组织中的表达

Expressions of HIF-α and its target gene in monochorionic twin placentas with twin-twin transfusion syndrome

目的:探讨缺氧诱导因子-1α(hypoxia-inducible factor 1α,HIF-1α)及其靶基因血管内皮细胞生长因子(vascular endothelial growth factor,VEGF)和血管内皮细胞生长因子受体-1(vascular endothelial growth factor-1,VEGFR-1)在双胎输血综合征(twin-to-twin transfusion syndrome,TTTS)患者胎盘组织中的表达。方法:双胎分娩后,取20例单绒毛膜双胎妊娠(其中TTTS 10例,未发生TTTS的对照组10例)两胎儿脐带下方胎盘组织,采用免疫组织化学方法对胎盘组织中HIF-1α及其靶基因VEGF和VEGFR-1蛋白进行定位检测;采用蛋白免疫印迹及RT-PCR方法对其蛋白及mRNA进行定量检测。结果:HIF-1α主要定位于滋养层细胞及绒毛内毛细血管的内皮细胞中;VEGF主要定位于滋养细胞、血管内皮细胞及绒毛间质细胞内;VEGFR-1主要定位在绒毛滋养细胞及血管内皮细胞内;TTTS胎盘组织中供血儿HIF-1α及其靶基因VEGF、VEGFR-1的蛋白及mRNA表达水平显著高于受血儿及对照组(P<0.001),而受血儿表达与对照组相比无明显变化(P>0.05),对照组间差异无统计学意义(P>0.05)。结论:在单绒毛膜双胎胎盘形成早期,局部HIF-1α、VEGF和VEGFR-1表达增高,可能影响胎盘血管生成并致TTTS的发生。

Objective： To determine hypoxia-inducible factor 1α（HIF-1α） and its target gene,vascular endothelial growth factor（VEGF） and receptor（VEGFR-1） concentrations in the placentas of the donor and recipient in monochorionic twin pregnancies with twin-twin transfusion syndrome（TTTS）.Methods： Twenty monochorionic twin pregnancy cases were included in the study（10 with and 10 without TTTS）.Tissue protein expressions of HIF-1α,VEGF and VEGFR-1 were determined by using immunohistochemistry.Western blot analysis were used to quantify and compare the protein expression.RT-PCR were used to compare their mRNA expressions.Results： HIF-1α was mainly observed in trophoblastic cells and villi capillaries endothelial cells,and VEGF in trophoblastic cells,endothelial cells and villi stromal cells;VEGFR-1 was mainly observed in villi trophoblastic cells and vascular endothelial cells.The placenta protein and mRNA expression of HIF-1α and its target gene in the donor placenta increased significantly（P0.001） compared with that in the control placenta,but the expression of HIF-1α and its target gene in the recipients tended to be similar in the controls（P0.05）.There was no difference between the controls.Conclusion： When the monochorionic twin placenta is formed in the early period,HIF-1α,VEGF and VEGFR-1 are over-expressed,which may affect the placenta angiogenesis and induce TTTS.