期刊
BIOLOGY OF REPRODUCTION
卷 99, 期 2, 页码 422-432出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/biolre/ioy025
关键词
inflammatory factor; low-dose aspirin; lipopolysaccharide; nuclear factor-kappa B; preeclampsia
资金
- National Natural Sciences Foundation [81490745]
- Major State Basic Research Development Program [2015CB943304]
Preeclampsia is a severe pregnancy-related disorder, and patients usually present with high circulating inflammatory factor levels and excessive activation of the nuclear factor-kappa B (NF-kappa B) pathway. Administration of aspirin (ASP) is effective for preventing preeclampsia, and thus, we propose that ASP might affect placental function by regulating the NF-kappa B pathway. Systemic lipopolysaccharide (LPS) (20 mu g/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-kappa B signaling in mice placentae induced by LPS was significantly reduced by ASP. In JEG-3 cells, LPS activated the NF-kappa B 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-kappa B 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-kappa B and its downstream signaling pathways in trophoblast cells. Summary Sentence Low-dose ASP is beneficial for preventing LPS-induced preeclampsia by inhibiting NF-kappa B and downstream signaling pathways in trophoblast cells.
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