摘要
目的通过对子痫前期及正常孕妇胎盘组织中解整合素金属蛋白酶19(ADAM19)的检测及ADAM19对绒毛滋养细胞分泌MMP2,9的调节,探讨ADAM19与子痫前期发病的关系。方法应用免疫组织化学(免疫组化)链霉素抗生物素-过氧化物酶法、免疫印迹技术和RT-PCR技术检测24例正常胎盘组织及46例子痫前期(其中26例为重度子痫前期,20例为轻度子痫前期)胎盘组织中ADAM19蛋白及mRNA的表达;用明胶酶谱方法检测抗ADAM19抗体作用后滋养细胞MMP2,9的分泌变化。结果胎盘组织中,ADAM19主要分布在多种滋养层细胞中,包括细胞滋养层细胞、合体滋养层细胞一和些绒毛间质结缔组织细胞、毛细血管中,其阳性信号不仅定位于细胞膜上,在细胞质中也有分布。正常胎盘中ADAM19的蛋白表达量为0.372±0.016,重度和轻度子痫前期组ADAM19蛋白定量分别为0.766±0.029和0.693±0.041,轻、重度子痫前期组分别与正常组比较,差异均有统计学意义(P<0.01),轻度子痫前期与重度子痫前期比较,差异无统计学意义(P>0.05)。ADAM19mRNA在正常组胎盘中的量为0.205±0.084,在重度和轻度子痫前期组中分别为0.481±0.057和0.454±0.033,轻、重度子痫前期组分别与正常组比较,差异均有统计学意义(P<0.01),轻度子痫前期与重度子痫前期比较,差异无统计学意义(P>0.05)。在体外培养的滋养层细胞中,100μg/L浓度的抗ADAM19抗体在作用12h即可以抑制滋养细胞MMP2,MMP9的分泌,其作用呈浓度依赖。结论子痫前期胎盘组织中ADAM19过表达可能与子痫前期的发生和发展有关;在子痫前期的发生中,ADAM19可能是在妊娠早期抑制滋养细胞的浸润而导致胎盘浅着床的。
Objective： To determine the expression of ADAM19 in the placenta of by cytotrophoblast, and to investigate the relationship between ADAM19 and pre - eclampsia. Methods： 24 samples of normal placenta and 46 of pre - eclamptic placenta （26 for late onset and 20 for early onset pre - eclampsia） were obtained. Immunohistochemistry, immunoblotting and RT - PCR were conducted to detect the expression and mRNA levels of ADAM19 in the placenta. Changes in MMP2 and MMP9 secreted by cytotrophoblasts were analyzed using gelatinase spectrum assay. Results： Positive expression signals of ADAM19 were detected both in cell membrane and cytoplasm, and distributed in various trophoblasts within the placenta, including cytotropboblasts, syncytiotrophoblasts, intervillous connective tissue cells and capillary vessels. The expression level of ADAM19 in normal placenta was significantly lower than that in late - onset and early - onset pre - eclampsia （ P 〈 0. 01 ）. The difference between late - onset and early - onset pre - eclampsia was not significant （ P 〉 0. 05）. The mRNA level of ADAM19 in normal placenta was significantly lower than that in late -onset and early - onset pre - eclampsia （ P 〈0. 01 ）. The difference between late - onset and early - onset pre - eclampsia was not significant （ P 〉 0. 05 ）. The secretion of MMP2 and MMP9 by In vitro cultured cytotrophoblasts was inhibited in a dose - dependent way after the treatment of 100μg/L anti - ADAM19 antibody for 12h. Conclusion： The over - expression of ADAM19 in the placenta of pre - eclampsia suggests that ADAM19 correlates with the occurrence and progression of preeclampsia. In the pathogenesis of pre -eclampsia, AD- AM19 may inhibit cytotrophoblast invasion in the early stages of pregnancy and can lead to abnormal placental implantation.
出处
《中国优生与遗传杂志》
2009年第7期28-31,共4页
Chinese Journal of Birth Health & Heredity
