Zhang Chunhua, Zhu Yong, Shen Yan, Zuo Changting
1 Department of Obstetrics and Gynaecology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.
2 The Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
Reprod Sci. 2018 Dec;25(12):1655-1662. doi: 10.1177/1933719118756746. Epub 2018 Feb 13.
Reduced expression of peroxisome proliferator-activated receptor γ (PPARγ) in the placenta was found in women with severe preeclampsia. Aspirin is currently used as the only recommended intervention in pregnancies for prevention of preeclampsia. In this study, we aimed to investigate whether aspirin could attenuate PPARγ inhibitor (T0070907)-induced preeclampsia and its impact on expression of PPARγ. Sixty Sprague-Dawley rats were used and treated with different doses of aspirin (0, 1, and 1.5 mg/kg) in presence or absence of PPARγ antagonist, T0070907. We found that mean arterial blood pressure was significantly reduced by aspirin treatment in T0070907-exposed rats. T0070907 exposure also led to significant decrease in fetal weight and increase in placental weights. However, 1.5 mg/kg of aspirin reversed these effects of T0070907. Additionally, aspirin also reversed T0070907-induced changes in the levels of thromboxane B2, vascular endothelial growth factor, soluble fms-like tyrosine kinase, and matrix metalloproteinase 2 in both maternal blood and placental tissue. The increased messenger RNA and protein levels of Cox1 and Cox2 induced by T0070907 were markedly reduced by aspirin treatment. Importantly, T0070907 repressed both transcriptional and translational levels of PPARγ, which were reversed by aspirin. In conclusion, this study suggests that aspirin prevented the occurrence of preeclampsia, which is possibly through enhancing both transcriptional and translational levels of PPARγ.
在重度子痫前期女性中发现,胎盘过氧化物酶体增殖物激活受体γ(PPARγ)的表达降低。目前,阿司匹林是唯一推荐用于预防子痫前期妊娠的干预措施。在本研究中,我们旨在探讨阿司匹林是否能减轻PPARγ抑制剂(T0070907)诱导的子痫前期及其对PPARγ表达的影响。我们使用了60只Sprague-Dawley大鼠,并在有或无PPARγ拮抗剂T0070907的情况下,用不同剂量的阿司匹林(0、1和1.5mg/kg)进行处理。我们发现,在暴露于T0070907的大鼠中,阿司匹林治疗可显著降低平均动脉血压。暴露于T0070907还导致胎儿体重显著下降和胎盘重量增加。然而,1.5mg/kg的阿司匹林可逆转T0070907的这些作用。此外,阿司匹林还逆转了T0070907诱导的母体血液和胎盘组织中血栓素B2、血管内皮生长因子、可溶性fms样酪氨酸激酶和基质金属蛋白酶2水平的变化。T0070907诱导的Cox1和Cox2信使核糖核酸和蛋白质水平升高,经阿司匹林治疗后明显降低。重要的是,T0070907抑制了PPARγ的转录和翻译水平,而阿司匹林可将其逆转。总之,本研究表明阿司匹林可预防子痫前期的发生,这可能是通过提高PPARγ的转录和翻译水平实现的。