Ameliorative effects of aspirin against lipopolysaccharide-induced preeclampsia-like symptoms in rats by inhibiting the pro-inflammatory pathway

Abstract

Preeclampsia is an inflammatory disease and has connection with increased pro-inflammatory cytokines. Aspirin reduces the incidence of preeclampsia complications. However, the effects of aspirin on lipopolysaccharide-induced preeclampsia-like symptoms in rats have not been reported and the underlying molecular mechanism has not been illuminated. Hence, we investigated the anti-inflammatory effects of aspirin on lipopolysaccharide-induced preeclampsia-like phenotypes in pregnant rats and elucidated the potential molecular mechanism. Preeclampsia-like phenotypes were induced by tail vein injection of lipopolysaccharide (1 μg/kg) on gestational day 14. Aspirin (2 mg/kg per day) were administered from gestational day 14 to 19. Clinical phenotypes were recorded. Placenta tissues and serum were obtained to measure inflammatory cytokines levels using ELISA kit on gestational day 20. The mRNA expressions of IL-6, IL-1β, and MCP-1 were measured by real-time PCR. Protein expressions including TLR4, MyD88, NF-κBp65, and TLR2 were determined by Western blot analysis in the rat placentas of each group. Aspirin obviously assuaged lipopolysaccharide-induced preeclampsia-like phenotypes in pregnant rats. Aspirin treatment significantly decreased the levels of pro-inflammatory cytokines in serum and placenta tissues of preeclampsia rats. Aspirin also obviously downregulated the mRNA expressions of IL-6, IL-1β, and MCP-1 and assuaged the activation of TLR4, MyD88, NF-κBp65, and TLR2 in the placental tissue. Our results indicated that aspirin could assuage preeclampsia-like phenotypes, and this improvement effect is possibly the result of the suppression of pro-inflammatory cytokines via the TLR4, MyD88, NF-κBp65, and TLR2 signaling pathway.

Astragaloside IV alleviates lipopolysaccharide‐induced preeclampsia‐like phenotypes via suppressing the inflammatory responses

“…And another report implied that TLR‐4/NF‐κB signaling pathway is involved in the development and pathogenesis of PE 40 . Consistent with previous studies, 8,9,18 we found an increase in placental TLR‐4 and NF‐κB expression in PE group. Importantly, AsIV treatment decreased TLR‐4 and NF‐κB protein expression in PE rats.…”

“…Beside the inflammation cytokines, in pregnant women with PE, antiangiogenic factor (soluble fms‐like tyrosine kinase‐1, sFlt‐1) is increased, whereas that of pro‐angiogenic factor (placenta growth factor, PIGF) is decreased 7 . Therefore, numerous studies have implied to employ angiogenic factors or inflammatory cytokines in the evaluation or diagnosis PE, 7 or even as a therapeutic target in the treatment of PE 8,9 …”

First Trimester Preeclampsia Screening and Prevention: Perspective in Chinese Mainland

“…69,70 Some studies have reported that aspirin may also prevent PE through anti-inflammatory effect by inhibiting the release of inflammatory factors in the placenta. 71,72 Recently, Li et al 73 investigated the impact of aspirin on gestational age advancement by metabolomics analysis and found that aspirin significantly slowed down metabolic gestational age by 1.27 weeks (95% CI: 0.66-1.88 weeks) in aspirin-treated high-risk women, compared to in those on placebo, and partially reversed various metabolic changes with the gestational age advancement.…”

Application of low dose aspirin in pre-eclampsia

“…Therefore, active anti-inflammatory makes sense in the prevention of pre-eclampsia. Sun et al ( 33 ) found that aspirin could improve the PE symptoms induced by lipopolysaccharide by inhibiting the release of inflammatory factors in the placenta and serum. The anti-inflammatory mechanism of aspirin may be the inhibition of microRNA (miR)-155/ nitric oxide synthase axis and the reduction of inflammatory factor production.…”

“…Aspirin reduced the production of inflammatory cytokines (interferon-γ and interleukin-8). Enhanced antioxidant capacity (increased activities of superoxide dismutase, catalase, and glutathione peroxidase) and adhesion of human decidual mesenchymal stem cells in term pre-eclampsia ( 33 ). Animal experiments have confirmed that aspirin may also exert anti-inflammatory effects by inhibiting NF-κB p65/TLRs/MyD88 signaling pathway and reducing the production of interleukin-6, 1β, tumor necrosis factor-α and interferon-γ ( 35 ).…”