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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24h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3d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24h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、24h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3d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、24h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3d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3d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 gamma-aminobutyric acid (GABA) receptor GABAA in the RVLM of PE rats and explore the effect of progesterone on cardiovascular function of PE rats The central mechanism of action. Methods Pregnant rats were treated with docetaxel acetate (DOCA) intraperitoneal injection and saline instead of normal drinking water to establish PE model. The mean arterial pressure, heart rate, renal sympathetic discharge activity (RSNA) Protein content and other indicators to verify the PE model was successfully established, that is pregnant rats + DOCA + saline group (PDS group), while the establishment of unprovoked rat group (Con group), unregulated rat + DOCA + saline group (DS group) , Pregnant rats (NP group). The NP group and the PDS group were divided into two subgroups and treated with progesterone (caproate, hydroxyprogesterone, 17-OHPC) and solvent (saline) respectively, which was NP + 17-OHPC group, NP + Veh group, PDS + 17-OHPC group and PDS + Veh group. The levels of progesterone in serum and cerebrospinal fluid of rats in each group were measured after 3 days of progesterone injection. The mean arterial pressure, heart rate, RSNA and 24h urinary protein levels in each group were measured. Western blotting was used to detect the expression of GABAA, GABAB receptor and nuclear progesterone receptor (nPGRA and nPGRB). Results Compared with Con group, DS group and NP group, mean arterial pressure, RSNA and PDGF group increased significantly (P <0.05). Compared with NP group, serum and cerebrospinal fluid (P <0.05). The levels of progesterone in serum and cerebrospinal fluid of PDS group were significantly increased (P <0.05), mean arterial pressure was decreased, RSNA was decreased, and proteinuria of 24h Decreased (P <0.05). The expression of GABAA receptor in RVLM of PDS group was lower than that of NP group (P <0.05), and the expression of GABAA receptor was upregulated after progesterone administration for 3d (P <0.05). The expression of nPGRB in PDS group was higher than that in NP group (P <0.05). The expression of nPGRB in PDS group was lower than that in NP group (P <0.05). The expression of GABAB receptor and nPGRA in RVLM of PDS rats had no significant difference with that of NP rats. Conclusions The expression of GABAA receptor is decreased in RVLM of PE rats, and the addition of progesterone can increase the expression of GABAA receptor in RV rats.