HIF-1α/VEGF在稽留流产患者绒毛组织中的表达及其与微血管密度的关系  

Expression of HIF-1α/VEGF in Villus Tissues of Missed Abortion Patients and Its Relationship with Microvessel Density

作　　者：石紫云[1] 张颖 折开娥[1] 刘飞飞 刘艳丽 袁晓华 SHI Zi-yun;ZHANG Ying;SHE Kai-e;LIU Fei-fei;LIU Yan-li;YUAN Xiao-hua(Department of Obstetrical,Shaanxi Provincial People's Hospital,Xi'an,Shaanxi,710068,China;Department of Obstetrical,The 986th Hospital of PLA Air Force,Xi'an,Shaanxi,710054,China)

机构地区：[1]陕西省人民医院产科,陕西西安710068 [2]空军第986医院南区妇产科,陕西西安710054

出　　处：《现代生物医学进展》2020年第7期1230-1235,共6页Progress in Modern Biomedicine

基　　金：国家自然科学基金青年科学基金项目(81200418);陕西省科技创新基地-科技资源开放共享平台项目(2018PT-12)。

摘　　要：目的:探讨缺氧诱导因子1α(HIF-1α)/血管内皮生长因子(VEGF)在稽留流产患者绒毛组织中的表达及其与微血管密度的关系。方法:采用免疫组织化学方法分别检测了30例人工流产和30例稽留流产患者绒毛组织的微血管密度(MVD)、HIF-1α和VEGF的表达。分别在缺氧(1%O2、5%CO2和94%N2)和常氧(20%O2、5%CO2和75%N2)条件下培养HTR8/SVneo细胞,并通过转染HIF-1αsi RNA来敲低HIF-1α。通过q RT-PCR和Western blot分析HTR8/SVneo细胞中HIF-1α和VEGF的m RNA和蛋白表达。此外,通过小管形成实验评价缺氧及转染HIF-1αsi RNA对HTR8/SVneo细胞小管形成的影响。结果:稽留流产组织样本中的MVD显著低于人工流产(7.22±0.55 vs 14.65±1.12,P<0.05)。HIF-1α和VEGF在稽留流产组织中的表达显著低于人工流产组织(P<0.05)。HIF-1α和VEGF的表达均与MVD显著正相关。与常氧相比,缺氧可显著上调HIF-1α和VEGF的m RNA和蛋白水平(P<0.05)。转染HIF-1αsi RNA显著下调HIF-1α和VEGF的m RNA和蛋白水平(P<0.05)。与常氧相比,缺氧可显著促进HTR8/SVneo细胞的小管形成(P<0.05),而转染HIF-1αsi RNA则可显著抑制显HTR8/SVneo细胞的小管形成(P<0.05)。结论:胎盘发育过程中的缺氧环境丢失及HIF-1α/VEGF的抑制可能是稽留流产发病的一项机制。Objective:To investigate the expression of HIF-1α/VEGF in villus tissues of patients with missed abortion and its relationship with microvessel density.Methods:Immunohistochemical method was used to detect the microvessel density(MVD),expression of HIF-1αand VEGF in villus tissue of 30 cases of induced abortion and 30 cases of missed abortion.HTR8/SVneo cells were cultured under hypoxic(1%O2,5%CO2,94%N2)and normoxic(20%O2,5%CO2,75%N2)conditions,respectively,and HIF-1αexpression was knocked down by transfection of HIF-1αsi RNA.The m RNA and protein expression of HIF-1αand VEGF in HTR8/SVneo cells were analyzed by q RT-PCR and Western blot.In addition,the effects of hypoxia and HIF-1αsi RNA on tubule formation of HTR8/SVneo cells were evaluated by tubule formation experiments.Results:The MVD in the missed abortion tissues was significantly lower than that of induced abortion tissues(7.22±0.55 vs 14.65±1.12,P<0.05).The expression of HIF-1αand VEGF in missed abortion tissues was significantly lower than that in induced abortion tissues(P<0.05).Both HIF-1αand VEGF expression were significantly positively correlated with MVD.Hypoxia significantly up-regulated the m RNA and protein levels of HIF-1αand VEGF compared with normoxia(P<0.05).Transfection of HIF-1αsi RNA significantly down-regulated the m RNA and protein levels of HIF-1αand VEGF(P<0.05).Compared with normoxia,hypoxia significantly promoted tubule formation in HTR8/SVneo cells(P<0.05),whereas transfection of HIF-1αsi RNA significantly inhibited tubule formation in HTR8/SVneo cells(P<0.05).Conclusions:Loss of hypoxic environment and inhibition of HIF-1α/VEGF during placental development may be a mechanism for the occurrence of missed abortion.

关 键 词：稽留流产 血管生成 缺氧 缺氧诱导因子-1Α 血管内皮生长因子 

分 类 号：R-33[医药卫生] R714.21