Abstract：
BACKGROUND: Preeclampsia (PE) is one of the leading causes of maternal and perinatal mortality and morbidity. Low-dose aspirin (LDA) is the most widely used drug to prevent PE, but the recommended dose of LDA varies according to different guidelines. Peroxisome proliferator-activated receptor (PPAR)-γ is involved in the formation of the placenta during pregnancy and is expressed in women with severe PE. In the present study, Our purpose was to investigate whether aspirin intervention in preeclampsia was related to PPAR-γ.
METHODS: We administered pregnant mice with PPAR-γ-specific antagonist(T0070907) 2 mg/kg/d at 8.5-12.5 days of pregnancy. Mice treated with T0070907 developed key features of preeclampsia. Two doses of LDA (10 mg/kg/d and 20 mg/kg/d) were administered to the mice with a PE phenotype for intervention.
RESULTS: LDA effectively decreased the increase in blood pressure in mice caused by T0070907 and decreased urinary protein levels and the urinary protein/creatinine ratio. LDA also inhibited the overexpression of endoglin and IL-β treated by T0070907. In addition, LDA evidently increased the placental weight and alleviates the degree of placental lesions of placenta and kidney. LDA alleviated the inhibition of PPAR-γ mRNA expression. The beneficial effect of 20 mg LDA was significantly better than that of 10 mg.
CONCLUSIONS: (1) LDA has a preventive effect against PE treated by PPAR-γ antagonist. (2) The preventive effect of LDA against PE is dose-dependent.
METHODS: We administered pregnant mice with PPAR-γ-specific antagonist(T0070907) 2 mg/kg/d at 8.5-12.5 days of pregnancy. Mice treated with T0070907 developed key features of preeclampsia. Two doses of LDA (10 mg/kg/d and 20 mg/kg/d) were administered to the mice with a PE phenotype for intervention.
RESULTS: LDA effectively decreased the increase in blood pressure in mice caused by T0070907 and decreased urinary protein levels and the urinary protein/creatinine ratio. LDA also inhibited the overexpression of endoglin and IL-β treated by T0070907. In addition, LDA evidently increased the placental weight and alleviates the degree of placental lesions of placenta and kidney. LDA alleviated the inhibition of PPAR-γ mRNA expression. The beneficial effect of 20 mg LDA was significantly better than that of 10 mg.
CONCLUSIONS: (1) LDA has a preventive effect against PE treated by PPAR-γ antagonist. (2) The preventive effect of LDA against PE is dose-dependent.
摘要：
背景：先兆子痫（PE）是孕产妇和围产期死亡率和发病率的主要原因之一。低剂量阿司匹林(LDA)是最广泛使用的预防PE的药物,但是LDA的推荐剂量根据不同的指南而有所不同。过氧化物酶体增殖物激活受体（PPAR）-γ参与妊娠期间胎盘的形成，并在患有严重PE的女性中表达。在本研究中,我们的目的是研究阿司匹林干预先兆子痫是否与PPAR-γ有关。
方法：我们在妊娠8.5-12.5天给妊娠小鼠施用PPAR-γ特异性拮抗剂（T0070907）2mg/kg/d。用T0070907治疗的小鼠出现先兆子痫的关键特征。向具有PE表型的小鼠施用两种剂量的LDA(10mg/kg/d和20mg/kg/d)用于干预。
结果：LDA有效降低了T0070907引起的小鼠血压升高，并降低了尿蛋白水平和尿蛋白/肌酐比值。LDA还抑制T0070907处理的内皮糖蛋白和IL-β的过表达。此外,LDA明显增加胎盘重量，减轻胎盘和肾脏的胎盘病变程度。LDA减轻了PPAR-γmRNA表达的抑制。20mgLDA的有益效果明显优于10mg。
结论：(1)LDA对PPAR-γ拮抗剂治疗PE有预防作用。(2)LDA对PE的预防作用呈剂量依赖性。
方法：我们在妊娠8.5-12.5天给妊娠小鼠施用PPAR-γ特异性拮抗剂（T0070907）2mg/kg/d。用T0070907治疗的小鼠出现先兆子痫的关键特征。向具有PE表型的小鼠施用两种剂量的LDA(10mg/kg/d和20mg/kg/d)用于干预。
结果：LDA有效降低了T0070907引起的小鼠血压升高，并降低了尿蛋白水平和尿蛋白/肌酐比值。LDA还抑制T0070907处理的内皮糖蛋白和IL-β的过表达。此外,LDA明显增加胎盘重量，减轻胎盘和肾脏的胎盘病变程度。LDA减轻了PPAR-γmRNA表达的抑制。20mgLDA的有益效果明显优于10mg。
结论：(1)LDA对PPAR-γ拮抗剂治疗PE有预防作用。(2)LDA对PE的预防作用呈剂量依赖性。
