血管内皮生长因子和胎盘微血管密度与胎盘植入发病的关系

Relationship between vascular endothelial growth factor and microvessel density in placenta and placenta increta

目的观察胎盘组织中血管内皮生长因子（vascular endothelial growth factor，VEGF）水平和胎盘微血管密度（microvessel density，MVD），探讨VEGF和MVD与胎盘植入发病的关系。方法选择2013年11月至2014年8月在福建省妇幼保健院定期产前检查并住院行剖宫产术分娩的单胎孕妇作为研究对象，纳入前置胎盘、胎盘植入及无并发症者（对照组）各10例进行研究。采集胎盘组织标本，以免疫组织化学、蛋白质印迹法、实时聚合酶链反应技术检测VEGF蛋白及其mRNA表达，并用免疫组织化学法检测胎盘MVD情况。采用f检验、秩和检验或KruskalWallis检验、单因素方差分析和Spearman相关性分析对数据行统计处理。结果（1）胎盘植入组和前置胎盘组孕妇人院时孕周和分娩孕周均早于对照组，差异有统计学意义（P值均〈0．05）。胎盘植入组与前置胎盘组和对照组比较，孕妇术中出血量多，手术时间和住院时间更长（P值均〈0．05）。（2）胎盘植入组、前置胎盘组、对照组胎盘组织中VEGF蛋白表达水平为（O．691±0．032）、（0．695±0．027）和（0．518±0．025）；VEGFmRNA相对含量为（1．667±0．661）、（1．832±0．678）及（0．767±0．269）。胎盘植入和前置胎盘组VEGF及其mRNA表达水平均高于对照组，差异有统计学意义（F值分别为373．401和27．399，P值均〈0．05），但前置胎盘组和胎盘植入组间差异无统计学意义（P值均〉0．05）。（3）胎盘植入组中，植入部位、交界部位和正常部位VEGF蛋白表达差异无统计学意义，但其mRNA分别为（2．519±0．116）、（1．482±0．232）及（1．000±0．000），呈递减趋势（F=240．827，P〈0．05）。（4）前置胎盘组中，脐带附着处、胎盘上缘及胎盘下缘VEGF蛋白表达水平分别为（0．702±0．026）、（0．698±0．026）及（0．685±0．029），均高于对照组的（0．528±0．020）、（0．519±0．035）及（0．509±0．010），差异均有统计学意义（t值分别为12．302、12．715和17．891，P值均〈0．05）；其mRNA水平分别为（2．080±0．539）、（1．587±0．757）及（1．828±0．704），均高于对照组的（1．024±0．272）、（0．546±0．083）及（0．731±0．157），差异有统计学意义（t值分别为8．093、2．401和4．259，P值均〈0．05）。（5）胎盘植入组和前置胎盘组MVD均高于对照组[分别为（171．2±14．7）、（155．7±14．6）和（147．8±12．3），F=7．277，P〈0．051。（6）胎盘植入组和对照组胎盘组织中的VEGF表达水平与MVD呈正相关（r=0．825，P〈0．05）。结论前置胎盘与胎盘植入的发生可能存在某些共同机制。胎盘VEGF表达水平上调和绒毛血管异常形成可能是胎盘植入发病的重要因素之一。

Objective To investigate the relationship between the expression level of vascular endothelial growth factor （VEGF） and microvessel density （MVD） in placenta tissue and placenta increta. Methods Thirty singleton pregnant women who received antenatal care and underwent cesarean section in Fujian Maternity and Child Health Hospital between November 2013 and August 2014, were enrolled in this study. They were divided into placenta previa group, placenta increta group and control group, with ten patients in each group. Placenta tissue was collected from each patient. Expressions of VEGF and its mRNA were detected by immunohistochemistry, Western blot, and real-time polymerase chain reaction. MVD in placenta tissue was measured by immunohistochemistry. Rank sum test, t test, Kruskal Wallis test, one-way ANOVA and Spearman correlation test were used for statistical analysis. Results （1） Gestational age at admission and delivery in placenta previa and placenta increta groups was lower than in control group （all P〈0.05）. Compared with control group, the placenta previa and placenta increta groups had more blood loss, and longer operating duration and hospital stay （all P〈0.05）. （2） The expression levels of VEGF and its mRNA in placenta increta and placenta previa groups were higher than in control group （VEGF： 0.691 ± 0.032, 0.695 ± 0.027 and 0.518± 0.025, respectively, F=373.401; VEGF mRNA： 1.667 ± 0.661, 1.832 ± 0.678 and 0.767 ± 0.269, respectively, F=27.399; both P〈0.05）. But there was no significant difference between placenta previa and increta groups. （3） There was no significant difference of VEGF expression in increta location, border site and normal site in placenta increta group, but its mRNA was decreasing （2.519 ± 0.116, 1.482 ± 0.232 and 1.000± 0.000, respectively, F=240.827, P〈0.05）. （4） Expression level of VEGF at the attachment of umbilical cord, upper and lower margin of placenta in placenta previa group was higher than in control group （0.702± 0.026 vs 0.528 ± 0.020, t=-12.302; 0.698 ±0.026 vs 0.519±0.035, t=-12.715; and 0.685±0.029 vs 0.509±0.010, respectively, t=17.891; all P〈0.05）. Expression of VEGF mRNA in placenta previa group was higher than in control group （2.080± 0.539 vs 1.024±0.272, t=8.093; 1.587±0.757 vs 0.546±0.083, t=2.401; 1.828±0.704 vs 0.731 ±0.157, t=-4.259; all P〈0.05）. （5） MVD in placenta increta group and placenta previa group was higher than in control group （171.2± 14.7, 155.7±14.6 vs 147.8 ± 12.3, respectively, F=7.277, P〈0.05）. （6） Expression level of VEGF in placenta increta group and control group was positively associated with MVD （r=0.825, P〈0.05）. Conclusions There may be some common mechanisms in the occurrence of placenta previa and placenta increta. Overexpression of VEGF in placenta and abnormal formation of villous vessels may be important factors in the pathogenesis of placenta increta.