孕激素上调子痫前期大鼠交感中枢γ-氨基丁酸A型受体表达

目的 观察γ-氨基丁酸（GABA）A型受体GABAA在子痫前期（PE）大鼠交感中枢头端延髓腹外侧区（RVLM）中的表达情况，探究孕激素改善PE大鼠心血管功能的中枢作用机制。方法 使用醋酸去氧皮质酮（DOCA）腹腔注射以及生理盐水（saline）替代普通饮用水的方法处理怀孕大鼠构建PE模型，通过监测平均动脉压、心率、肾交感放电活动（RSNA）及24 h尿蛋白含量等指标验证PE模型成功建立，即为受孕大鼠+DOCA+saline组（PDS组），同时设立未孕大鼠组（Con组）、未孕大鼠+DOCA+saline组（DS组）、受孕大鼠组（NP组）。将NP组及PDS组大鼠各分出两个亚组，分别予以孕激素（己酸羟孕酮，17-OHPC）处理和溶剂（生理盐水）对照处理，即为NP+17-OHPC组、NP+Veh组、PDS+17-OHPC组和PDS+Veh组。孕激素腹腔注射3 d后，检测各组大鼠血清及脑脊液中孕激素含量，监测各组大鼠的平均动脉压、心率、RSNA以及检测24 h尿蛋白含量。蛋白质印迹法检测GABAA、GABAB受体以及核孕激素受体（nPGRA和nPGRB）蛋白的表达水平。结果 与Con组、DS组和NP组相比，PDS组大鼠平均动脉压升高、RSNA增强、24 h尿蛋白含量增加（P<0.05）；与NP组相比，PDS组大鼠血清及脑脊液中孕激素含量均降低（P<0.05）；PDS组大鼠补充孕激素3 d后，血清及脑脊液中孕激素含量均升高（P<0.05），平均动脉压下降、RSNA减弱、24 h尿蛋白含量降低（P<0.05）。PDS组大鼠RVLM内GABAA受体表达较NP组减少（P<0.05），补充孕激素3 d后表达上调（P<0.05）。nPGRB在PDS组大鼠RVLM内表达高于NP组（P<0.05），补充孕激素3 d后其在PDS组内表达降低（P<0.05）。GABAB受体和nPGRA在PDS组大鼠RVLM内的表达与NP组差异无统计学意义。结论 GABAA受体在PE大鼠RVLM内表达降低，补充孕激素可增加PE大鼠RVLM内GABAA受体的表达。
Objective To observe the expression of GABAA receptor in rostral ventrolateral medulla (RVLM) of preeclampsia (PE) rats, so as to explore the role of GABAA receptor in the mechanisms by which progesterone improves cardiovascular dysfunction in PE rats. Methods Desoxycorticosterone acetate (DOCA) was intraperitoneally injected and 0.9% normal saline (NS) replaced the normal drinking water in pregnant rats to establish rat PE model, and the models were verified by measuring the mean arterial pressure (MAP), heart rate (HR), renal sympathetic nerve activity (RSNA), and concentration of 24-h urine protein. And the model rats were set as pregnant+DOCA+saline (PDS) group. The other three groups included the nonpregnant rats (Con) group, nonpregnant rats receiving DOCA and saline (DS) group, and normal pregnant rats (NP) group. The PDS and NP groups were further divided into two subgroups according to different treatments:progesterone (17-OHPC) or NS administration, and the four groups were designated as NP+17-OHPC, NP+Veh, PDS+17-OHPC and PDS+Veh groups. After three days of 17-OHPC treatment, the levels of progesterone in serum and cerebrospinal fluid were examined by the enzyme-linked immunosorbent assay (ELISA). The MAP,HR, RSNA and the 24-h urine protein were measured. Western blotting analysis was used to detect the protein expressions of GABAA receptor, GABAB receptor, and the nuclear progesterone receptors (nPGRA and nPGRB). Results Compared with Con, DS and NP groups, the MAP, RSNA and 24-h urine protein were increased significantly in PDS group (P<0.05). Compared with NP group, progesterone levels in the serum and cerebrospinal fluid were significantly