先兆子痫大鼠循环、胎盘及肾脏局部血管紧张素Ⅱ及其1型受体的表达

Expression of angiotensin Ⅱ and its type 1 receptor in circulation, placenta and kidney of the preeclampsia rat model

目的研究先兆子痫大鼠模型循环系统、胎盘及肾脏局部血管紧张素Ⅱ（AngⅡ）及其1型受体（AT1）的表达。方法采用一氧化氮合酶抑制剂亚硝基左旋精氨酸甲酯（L—NAME）制备大鼠先兆子痫模型，分别比较先兆子痫大鼠、正常妊娠大鼠、未孕对照组大鼠动脉收缩压（SBP）、尿蛋白量（24h）、肝肾功能，并对各组大鼠肾组织进行光镜检查。ELISA法和放射性免疫法分别测定各组大鼠血浆及肾脏局部匀浆液AngⅡ水平。Western印迹法检测大鼠胎盘局部AT1表达。免疫组化法及Western印迹法测定大鼠肾脏局部AT1的表达。结果在先兆子痫大鼠中，SBP及尿蛋白量（24h）均较未孕对照组显著升高（P〈0．05）。先兆子痫大鼠血浆AngⅡ显著高于正常妊娠组[（0．706±O．086）ng／L比（0．540±0．085）ng／L，P〈0．05]；胎盘局部AT1表达比正常妊娠组升高46％（P〈0．05）；肾脏局部AngⅡ明显低于正常妊娠组[（65．543±40．634）ng／g比（165．543±33．078）ng／g，P〈0．05）；肾脏AT1表达减少，仅为正常妊娠组及未孕对照组的33％及59％（P〈0．05）。结论先兆子痫中，胎盘局部RAS表达增强，循环AngⅡ表达增高，肾脏局部RAS表达下调。

Objective To investigate the expression of angiotensinⅡ （Ang Ⅱ ） and its type 1 receptor （AT1） in circulation, placenta and kidney of the rats preeelampsia. Methods Preeclampsia rat model was developed by inhibitor of nitric oxide synthase （L-NAME）. The systolic blood pressure （SBP）, 24 h urine protein, hepatic and renal function were compared among the preeclampsia group, the normal pregnant group and nonpregnant control group. The kidney tissue was observed by light microscopy. ELISA and radioimmunoassay were used to detect Ang Ⅱ in rat plasma and kidney homogenate respectively. Placental AT1 was measured by Western blot. The level of kidney AT1 was evaluated by immunohistochemistry and Western blot. Results In preeclampsia rats, SBP and 24 h urine protein were significantly higher compared with control groups. Compared to normal pregnant group, plasma Ang Ⅱ of preeelampsia rats was much higher [（0.706±0.086） ng/L vs （0.540±0.085） ng/L, P〈0.05]; placental AT1 was increased by 46%（P〈 0.05）; kidney Ang Ⅱ was decreased signigicantly [（65.543±40.634） ng/g vs （165.543±33.078） ng/g, P〈0.05]. The expression of AT1 in kidney of preeclampsia rats was reduced evidently,which was only 33% of normal pregnancy group and 59% of nonpregnant control group,respectively （P〈0.05）. Conclusions In preeclampsia rat model, the circulating Ang Ⅱ is increased, the placental RAS is activated, while the kidney RAS is suppressed. The underlying mechanism of proteinuria and kidney damage associated with this phenomenon in preeelampsia needs further research.