石紫云,张 颖,折开娥,刘飞飞,刘艳丽,袁晓华.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[J].,2020,(7):1230-1235 |
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 |
投稿时间:2019-10-23 修订日期:2019-11-18 |
DOI:10.13241/j.cnki.pmb.2020.07.006 |
中文关键词: 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 |
英文关键词: Missed abortion Angiogenesis Hypoxia Hypoxia-inducible factor-1α Vascular endothelial growth factor |
基金项目: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) |
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中文摘要: |
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-1α siRNA来敲低HIF-1α。通过qRT-PCR和Western blot分析HTR8/SVneo细胞中HIF-1α和VEGF的mRNA和蛋白表达。此外,通过小管形成实验评价缺氧及转染HIF-1α siRNA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mRNA和蛋白水平(P<0.05)。转染HIF-1α siRNA显著下调HIF-1α和VEGF的mRNA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-1α siRNA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。 |
英文摘要: |
ABSTRACT 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-1α and 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-1α expression was knocked down by transfection of HIF-1α siRNA. The mRNA and protein expression of HIF-1 α and VEGF in HTR8/SVneo cells were analyzed by qRT-PCR and Western blot. In addition, the effects of hypoxia and HIF-1 α siRNA 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-1α and VEGF in missed abortion tissues was significantly lower than that in induced abortion tissues (P<0.05). Both HIF-1α and VEGF expression were significantly positively correlated with MVD. Hypoxia significantly up-regulated the mRNA and protein levels of HIF-1α and VEGF compared with normoxia (P<0.05). Transfection of HIF-1α siRNA significantly down-regulated the mRNA and protein levels of HIF-1α and VEGF (P<0.05). Compared with normoxia, hypoxia significantly promoted tubule formation in HTR8/SVneo cells (P<0.05), whereas transfection of HIF-1α siRNA significantly inhibited tubule formation in HTR8/SVneo cells (P<0.05). Conclusion: Loss of hypoxic environment and inhibition of HIF-1α/VEGF during placental development may be a mechanism for the occurrence of missed abortion. |
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