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.
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。