腺苷A1受体在妊娠期高血压以及子痫前期中的作用

目的 探讨腺苷A1受体(A1R)在妊娠期高血压以及子痫前期发病机制中的作用.方法 取剖宫产分娩的妊娠期高血压(n=6)、子痫前期(n=14)和正常对照(n=15)产妇胎盘组织,采用免疫荧光检测A1R在胎盘组织中的表达部位,蛋白质印迹法检测A1R在胎盘中的表达量.建立常氧、缺氧(8、24、48、72 h)以及缺氧复氧(8 h)滋养细胞模型,运用实时荧光定量PCR和蛋白质印迹法检测A1R在细胞中的表达情况,Transwell和蛋白质印迹法检测加入A1R拮抗剂8-环戊基-1,3-二丙基黄嘌呤(DPCPX)后对缺氧的胎盘滋养细胞侵袭性和蛋白激酶A(PKA)表达的影响.结果 A1R在胎盘表面的滋养细胞以及内皮细胞中均有表达.与正常胎盘比较,A1R在轻度和重度子痫前期胎盘组织中表达升高(P＜0.01).A1R在体外胎盘滋养细胞缺氧模型中的表达随着缺氧时间的延长而逐渐升高(P＜0.05).胎盘滋养细胞缺氧模型中滋养细胞的侵袭能力较正常组下降(P＜0.01),PKA表达下降(P＜0.05);加入拮抗剂DPCPX可以增强滋养细胞的侵袭性(P＜0.05),同时上调PKA的表达水平(P＜0.05).结论 缺氧程度的增加可以使A1R表达升高,A1R在胎盘滋养细胞中的作用机制可能与调节PKA相关.

Role of adenosine A1 receptor in gestational hypertension and preeclampsia

Objective To study the role of A1R(adenosine A1 receptor)in trophoblastic cells of gestational hypertention, pre-eclampsia and the potential mechanism. Methods The location of A1R protein in placenta tissues were detected by immunofluorescence technique. A1R protein expression in placenta tissues were detected by western blot. A1R mRNA and protein expression in trophoblastic cells were detected by qt-PCR and Western blot respectively. A1R was inhibited in trophoblastic cells. Invasion ability of cells were examined by transwell invasion assay. Expression of PKA protein was detected by western blot. Results We found that A1R protein overexpressed in extravillous trophoblastic cells and vascular endothelial cell. In mild and sever pre-eclampsia placenta, A1R expression was higher than it of normal placenta tussies. In the hypoxia model of trophoblastic cells, A1R was found lower than it of negative control. However, it increased according to hypoxia time. In the hypoxia model of trophoblastic cells, the invasion of trophoblastic cells is lower than that of negative control. Conclusion These results indicated that the expression of A1R is elevated according to hypoxia time. Inhibiting A1R promotes trophoblastic cells invasion and PKA. The role of A1R in trophoblastic cells may related to PKA.