Grupo Reproducción, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
Red Iberoamericana de Alteraciones Vasculares Asociadas a Transtornos del Embarazo (RIVA-TREM), Chillán, Chile.
Am J Reprod Immunol. 2020 Feb;83(2):e13207. doi: 10.1111/aji.13207. Epub 2019 Nov 26.
Oxidative stress and inflammation are key events leading to pre-eclampsia, involved in several maternal deaths. Low doses of acetylsalicylic acid (ASA) are used in the prevention and treatment of pre-eclampsia. The synthesis of aspirin-triggered lipoxin (ATL) by cyclooxygenase-2 acetylation is an alternative mechanism of ASA, which could explain the effectiveness of ASA treatments. The aim of this study was to evaluate the role of ASA, salicylates, and ATL in the modulation of the oxidative and inflammatory responses induced by plasma from women with pre-eclampsia.
Plasma from 14 women with pre-eclampsia and 17 normotensive pregnant women was probed for inducing oxidative and inflammatory responses on endothelial cells and U937 promonocytes. The role of ATL, ASA, and salicylic acid (SA) on these events was evaluated.
Plasma from women with pre-eclampsia induced TBARS and nitrotyrosine production on endothelial and U937 cells. Pre-treatment with both ATL and ASA decreased the TBARS production, while ATL decreased the nitrotyrosine. Pre-eclamptic plasma augmented the translocation of NF-kB on U937 cells, which decreased by a high dose of ASA and SA. Finally, the pre-eclamptic plasma increased the adhesion of leukocytes-PMN and monocytes-to endothelium, and we were able to determine a state of resolution of inflammation, since ATL decreased the PMN adhesion, and conversely, it increased the monocytes adhesion to endothelium.
Together, these results suggest that ATL could explain the beneficial actions of ASA and support further research on mechanisms, real efficacy, and rational use of ASA in pre-eclampsia.
氧化应激和炎症是导致子痫前期的关键事件，与一些产妇死亡有关。低剂量乙酰水杨酸（ASA）用于子痫前期的预防和治疗。环氧化酶-2乙酰化合成阿司匹林触发的脂氧素（ATL）是 ASA 的另一种作用机制，这可以解释 ASA 治疗的有效性。本研究旨在评估 ASA、水杨酸盐和 ATL 在调节子痫前期妇女血浆诱导的氧化和炎症反应中的作用。
用 14 例子痫前期妇女和 17 例正常妊娠妇女的血浆探测诱导内皮细胞和 U937 前单核细胞发生氧化和炎症反应。评估了 ATL、ASA 和水杨酸（SA）在这些事件中的作用。
子痫前期妇女的血浆诱导内皮细胞和 U937 细胞产生 TBARS 和硝基酪氨酸。ATL 和 ASA 的预处理均降低了 TBARS 的产生，而 ATL 降低了硝基酪氨酸。子痫前期血浆增加了 U937 细胞 NF-kB 的易位，而高剂量的 ASA 和 SA 则减少了易位。最后，子痫前期血浆增加了白细胞-PMN 和单核细胞与内皮的黏附，我们能够确定炎症的消退状态，因为 ATL 降低了 PMN 的黏附，相反，它增加了单核细胞与内皮的黏附。
综上所述，这些结果表明 ATL 可以解释 ASA 的有益作用，并支持进一步研究 ASA 在子痫前期中的作用机制、真实疗效和合理应用。
