15-epi-lipoxin A4 reduces the mortality of prematurely born pups in a mouse model of infection-induced preterm birth.

15-epi-lipoxin A4 reduces the mortality of prematurely born pups in a mouse model of infection-induced preterm birth.
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DOI:
10.1093/molehr/gau117
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发表时间:
2015-04
影响因子:
4
通讯作者:
Norman JE
Norman JE
中科院分区:
医学2区
文献类型:
--
作者:
Rinaldi SF;Catalano RD;Wade J;Rossi AG;Norman JE

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早产仍然是新生儿死亡率和全球发病率的主要原因。为了减少与早产相关的死亡率和发病率。 PTL使用感染诱导的PTL的小鼠模型,我们研究了15-EPI脂蛋白A4是否可以延迟脂多糖(LPS)诱导的PTL,并在妊娠小鼠的D17上降低了PTL(N = 9-12)。载体或PBS宫内施用之前的15-EPI脂蛋白A4。与单独接受LPS相比,在接受LPS治疗之前用15-EPI脂蛋白A4治疗的小鼠中的36小时内(p <0.05)(p <0.05)。 H后处理表明,15- EPI脂蛋白A4治疗增加了子宫,胎盘和胎儿膜(p <0.05)(p <0.05)的PTGS2表达(p <0.05),并增加了子宫和子宫中15- hpgd的表达(p <0.05),这表明15--表脂蛋白A4可以调节前列腺素的局部产生和活性,这表明脂肪毒素水平增加可能是治疗PTL的一种有用的新型热选择,从而保护了胎儿免受感染诱发的早产的不良影响。
Preterm birth remains the leading cause of neonatal mortality and morbidity worldwide. There are currently few effective therapies and therefore an urgent need for novel treatments. Although there is much focus on trying to alter gestation of delivery, the primary aim of preterm birth prevention therapies should be to reduce prematurity related mortality and morbidity. Given the link between intrauterine infection and inflammation and preterm labour (PTL), we hypothesized that administration of lipoxins, key anti-inflammatory and pro-resolution mediators, could be a useful novel treatment for PTL. Using a mouse model of infection-induced PTL, we investigated whether 15-epi-lipoxin A4 could delay lipopolysaccharide (LPS)-induced PTL and reduce pup mortality. On D17 of gestation mice (n = 9–12) were pretreated with vehicle or 15-epi-lipoxin A4 prior to intrauterine administration of LPS or PBS. Although pretreatment with 15-epi-lipoxin A4 did not delay LPS-induced PTL, there was a significant reduction in the mortality amongst prematurely delivered pups (defined as delivery within 36 h of surgery) in mice treated with 15-epi-lipoxin A4 prior to LPS treatment, compared with those receiving LPS alone (P < 0.05). Quantitative real-time (QRT)-PCR analysis of utero-placental tissues harvested 6 h post-treatment demonstrated that 15-epi-lipoxin A4 treatment increased Ptgs2 expression in the uterus, placenta and fetal membranes (P < 0.05) and decreased 15-Hpgd expression (P < 0.05) in the placenta and uterus, suggesting that 15-epi-lipoxin A4 may regulate the local production and activity of prostaglandins. These data suggest that augmenting lipoxin levels could be a useful novel therapeutic option in the treatment of PTL, protecting the fetus from the adverse effects of infection-induced preterm birth.
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