低剂量阿司匹林对过氧化物酶体增殖物激活受体-γ拮抗剂治疗子痫前期小鼠模型的预防作用。
The preventive effect of low-dose aspirin in a PPAR-γ antagonist treated mouse model of preeclampsia.
机构信息
Department of Obstetrics and Gynecology, Peking University First Hospital, No. 8 Sishku Street, Xicheng District, Beijing, 100034, PR China.
出版信息
BMC Pregnancy Childbirth. 2022 Jul 29;22(1):606. doi: 10.1186/s12884-022-04901-x.
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.
背景
子痫前期（PE）是孕产妇和围产儿发病率和死亡率的主要原因之一。小剂量阿司匹林（LDA）是预防 PE 最常用的药物，但 LDA 的推荐剂量因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。本研究旨在探讨阿司匹林干预子痫前期是否与 PPAR-γ有关。
方法
我们在妊娠 8.5-12.5 天时给怀孕的小鼠每天给予 2mg/kg/d 的 PPAR-γ 特异性拮抗剂（T0070907）。用 T0070907 处理的小鼠出现子痫前期的关键特征。对具有 PE 表型的小鼠给予两种剂量的 LDA（10mg/kg/d 和 20mg/kg/d）进行干预。
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 还抑制了 T0070907 处理的内胚层蛋白和 IL-β的过表达。此外，LDA 明显增加了胎盘重量，并减轻了胎盘和肾脏的胎盘病变程度。LDA 缓解了 PPAR-γ mRNA 表达的抑制。20mg LDA 的有益效果明显优于 10mg。
结论
（1）LDA 对 PPAR-γ 拮抗剂治疗的 PE 具有预防作用。（2）LDA 对 PE 的预防作用呈剂量依赖性。
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