GPR30在胎盘组织中的差异表达及其与子痫前期的关系

Different expressions of GPR30 in placental tissues and their relationship with preeclampsia

摘要:

目的：探讨胎盘组织中新型雌激素受体G-蛋白偶联受体30（g-protein coupled receptor 30，GPR30）的表达及其与子痫前期（preeclampsia，PE）发病的关系。方法：收集重庆医科大学附属第一医院2012年1月至2014年5月分娩的20例PE和19例正常产妇的胎盘组织，应用免疫组化方法检测GPR30在胎盘组织中的表达。然后以人脐静脉血管内皮细胞建立PE细胞模型，以免疫荧光技术和蛋白印迹技术（Western blot）检测GPR30蛋白的表达情况。以流式细胞仪检测凋亡、以体外小管形成实验检测管腔成形能力、以迁移实验检测迁移能力等。结果：GPR30在PE组胎盘组织中表达明显低于对照组（P=0.000）；而在细胞模型中，经缺氧/复氧处理后，GPR30蛋白的表达降低（P=0.000）；GPR30抑制剂-G15处理使其凋亡增加（P=0.000）；而GPR30激动剂-G1能促进其管腔成形（P=0.000）和迁移（P=0.0015），同时，G15能抑制17β-雌二醇对其管腔成形（P=0.03９）和迁移（P=0.014）的保护作用。结论：GPR30表达下降可能与PE胎盘血管内皮细胞的功能异常相关。

Abstract:

Objective：To evaluate the different expressions of GPR30 in placenta tissues，and their relationship with the pathogenesis of preeclampsia. Methods：Twenty cases of preeclampsia and 19 cases of normal maternal placental tissues were collected in the First Affiliated Hospital of Chongqing Medical University from January 2012 to May 2014. Immunohistochemistry was used to detect the expression of GPR30 in the placental tissues. Human umbilical vein endothelial cells（HUVECs） were used as a cell model of preeclampsia. Immunofluorescence and Western blot were used to detect the expression of GPR30 protein in HUVECs. Flow cytometry was used to detect the apoptosis of HUVECs. In vitro tube formation assay was used to detect capability of the tube formation of HUVECs and migration assay was used to detect the migration ability of HUVECs. Results：The expression of GPR30 in placental vascular endothelial cells was lower in the preeclamptic placentas than in normo-tensive controls. The expression of GPR30 protein was reduced in HUVEC after hypoxia/reoxygenation（H/R） treatment. The apoptosis of HUVECs was increased with the treatment of inhibitor of GPR30-G15. The GPR30 agonist-G1and 17β-estradiol（E2） exerted protective effects on H/R-exposed HUVECs by pro－tecting the capabilities of the tube formation and migration；this effect was abolished by G15. Conclusion：Declined expression of GPR30 may play an important role in placental endothelial dysfunction in preeclampsia.