低分子肝素对胎儿生长受限患者胎盘超微结构及血管内皮生长因子表达的影响

Effects of low-molecular weight heparin on the placental ultrastructure and VEGF expression in cases with fetal growth restriction

目的探讨低分子肝素对胎儿生长受限(fetal growth restriction,FGR)胎盘组织超微结构及血管内皮生长因子(vascular endothelial growth factor,VEGF)的表达及低分子肝素治疗FGR的机理。方法选择2010年5月至2011年12月北京大学第三医院妇产科收治的资料完整的FGR患者88例,分为肝素治疗组(47例)、常规治疗组(29例)和对照组(12例),采用透射电镜方法观察各组胎盘的超微结构的变化及免疫组织化学SP法检测胎盘组织中VEGF的表达。结果①肝素治疗组胎盘合体滋养细胞表面有大量排列整齐的微绒毛,细胞质内含丰富的粗面内质网和线粒体,细胞核形态规则,核染色质致密且分布均匀,绒毛间质内有少量胶原纤维,毛细血管扩张。②肝素治疗组滋养细胞、绒毛间质细胞和血管内皮细胞VEGF蛋白表达水平(111.5±5.9、160.2±7.8和161.9±5.4)与对照组(147.8±5.3、181.4±5.1和187.1±7.5)比较,差异有统计学意义(P<0.01)。常规治疗组绒毛间质细胞VEGF蛋白表达水平(168.7±7.1)与对照组(181.4±5.1)比较,差异有统计学意义(P<0.05)。结论低分子肝素可改善胎盘组织的超微结构,增强胎盘VEGF蛋白的表达,促进胎盘微血管的通透性,治疗FGR。

Objective To investigate the effect of lowmolecular- weight heparin on FGR and its relation with expression of VEGF and the morphology of the placental ultrastructure. Methods 47 cases of FGR were enrolled in low- molecular- weight heparin group, 29 cases of FGR were enrolled routine treatment group and 12 ca- ses of FGR were in control group. Electron microscope was used to study the placental ultrastructure changes. The expression of vascular endothelial growth factor （VEGF） was measured by immunohistochamistry method. Results The abnormal changes of placenta in routine treatment group was ruptured microvillus, endoplasmic reticulum expansion and vacuolization, and capillary crimpled. While in low- molecular- weight heparin group, normal nuclear structure and cellular organelle were found. The position of VEGF in placenta tissue was in the sycytiotrophoblast, the interstitial cells of villus and endothelial cells. The expression of VEGF in low- molecular- weight heparin group in the sycytiotrophoblast, the interstitial cells of villus and endothelial cells was （111.5± 5.9, 160.2± 7.81 and 61.9± 5.4）, which were higher than that in the control group （147.8± 5.3, 181.4± 5.1 and 187.1± 7.5） respeactely （P〈0. 01）. Conclusion Low- molecular - weight heparin can improve the placental ultrastructure and increase the expression of VEGF in FGR.