601. The intervention effect of aspirin on a lipopolysaccharide-induced preeclampsia-like mouse model by inhibiting the nuclear factor-κB pathway.
- Author
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Li G, Ma L, Lin L, Wang YL, and Yang H
- Subjects
- Animals, Aspirin therapeutic use, Cell Line, Tumor, Cyclooxygenase Inhibitors therapeutic use, Disease Models, Animal, Female, Interleukin-6 blood, Lipopolysaccharides, Mice, Placenta metabolism, Pre-Eclampsia chemically induced, Pre-Eclampsia metabolism, Pregnancy, Tumor Necrosis Factor-alpha blood, Vascular Endothelial Growth Factor Receptor-1 blood, Aspirin pharmacology, Cyclooxygenase Inhibitors pharmacology, NF-kappa B metabolism, Placenta drug effects, Pre-Eclampsia drug therapy, Signal Transduction drug effects
- Abstract
Preeclampsia is a severe pregnancy-related disorder, and patients usually present with high circulating inflammatory factor levels and excessive activation of the nuclear factor-κB (NF-κB) pathway. Administration of aspirin (ASP) is effective for preventing preeclampsia, and thus, we propose that ASP might affect placental function by regulating the NF-κB pathway. Systemic lipopolysaccharide (LPS) (20 μg/kg) was used to induce preeclampsia-like pregnant mouse model, and low-dose ASP (15.2 mg/kg) was administrated. Here, we report significantly increased circulatory expression levels of the proinflammatory cytokines tumor necrosis factor-alpha, interleukin-6, and soluble Fms-related tyrosine kinase-1 in LPS-treated pregnant mice, accompanied by kidney and placental dysfunction. Low-dose ASP treatment significantly reversed the preeclampsia-like phenotype, lowering hypertension, decreasing proteinuria, and ameliorating fetal growth retardation. Moreover, the excessive activation of NF-κB signaling in mice placentae induced by LPS was significantly reduced by ASP. In JEG-3 cells, LPS activated the NF-κB signaling pathway by upregulating the expression of cyclooxygenase-2 (COX-2) and related inflammatory factors, whereas the invasion ability of JEG-3 cells was weakened. However, ASP administration impeded NF-κB signaling activation, downregulated COX-2 and inflammatory factor expression, and rescued trophoblast invasion. This study provides new evidence that low-dose ASP is beneficial for preeclampsia prevention by inhibiting NF-κB and its downstream signaling pathways in trophoblast cells.
- Published
- 2018
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