Quercetin Prevents Lipopolysaccharide-Induced Experimental Preterm Labor in Mice and Increases Offspring Survival Rate
Quercetin Prevents Lipopolysaccharide-Induced Experimental Preterm Labor in Mice and Increases Offspring Survival Rate
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槲皮素可预防脂多糖诱导的小鼠实验性早产并提高后代存活率
DOI：
10.1007/s43032-019-00034-3
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发表时间：
2020-03-10
影响因子：
2.9
通讯作者：
Zhang, Weishe
中科院分区：
文献类型：
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作者：
Lin, Xinxiu;Peng, Qiaozhen;Zhang, Weishe
早产仍然是一个世界性问题，造成严重的社会经济负担和家庭负担。目前，还没有有效的方法来预防早产。由于炎症会增加早产的风险，而槲皮素被报道具有抗炎、增强免疫和抗氧化的作用，因此本研究旨在探讨是否有抑制早产和提高子代存活率的作用。脂多糖是早产炎性动物模型中常用的药物之一。在妊娠第15天，小鼠经口灌胃给予一定剂量的磷酸盐缓冲盐水(PBS)或一定剂量的槲皮素(低浓度，30 mg/kg；中浓度，90 mg/kg；高浓度，150 mg/kg)。2小时后，小鼠腹腔注射脂多糖(50μg/kg)或赋形剂(Ip)。在没有槲皮素的情况下，在内毒素处理的小鼠中观察到100%的早产发生率，并且胎儿全部死亡。中浓度的槲皮素可显著抑制63.5%的脂多糖诱导的炎性早产，22日龄仔鼠存活率为83.76%。在mRNA水平上显著抑制脂多糖诱导的小鼠子宫肌层中核因子-kappa-B/p65(RelA)、AP-1/C-jun(Jun)、环氧合酶-2(Ptgs2)和白介素6(IL6)的表达，在蛋白水平上抑制p65和C-jun的表达。基于以上观察，我们得出结论：槲皮素能抑制脂多糖诱导的小鼠早产，并通过影响核因子-κB/AP-1途径提高子代存活率。
Premature labor is still a worldwide problem, causing serious social economic burden and family burden. Currently, there is no effective way to prevent preterm labor. Since inflammation increases the risk of preterm birth and quercetin is reported to have anti-inflammation, immune-enhancement, and antioxidative effects, this study aims to explore whether quercetin exerts inhibitory effect on preterm labor in mice and increases offspring survival. Lipopolysaccharide (LPS) is one of the commonly used drugs in the inflammatory animal model of preterm birth. On day 15 of pregnancy, mice received a dose of vehicle phosphate-buffered saline (PBS) or a dose of quercetin (low concentration, 30 mg/kg; medium concentration, 90 mg/kg; high concentrations, 150 mg/kg) via oral gavage. After 2 h, mice received a dose of LPS (50 μg/kg) or vehicle intraperitoneally (i.p.). In the absence of quercetin, a 100% incidence of preterm labor was observed in LPS-treated mice, and the fetuses were all died. Medium concentration of quercetin significantly prevented 63.5% of LPS-induced inflammatory preterm labor, and the survival rate of pups on day 22 was 83.76%. Specifically, quercetin significantly inhibited LPS-induced upregulation of NF-kappa-B/P65(RELA), AP-1/C-JUN(JUN), cyclooxygenase-2(PTGS2), and interleukin 6(IL6) in mice myometrium on mRNA level and inhibited the upregulation of P65 and C-JUN on protein level. Based on these observations, we concluded that quercetin exerts inhibitory effect on LPS-induced experimental mice preterm labor and increases offspring survival through a mechanism involving NF-κB/AP-1 pathway.