Dual effect of nitric oxide on uterine prostaglandin synthesis in a murine model of preterm labour
Dual effect of nitric oxide on uterine prostaglandin synthesis in a murine model of preterm labour
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DOI：
10.1111/j.1476-5381.2010.00911.x
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发表时间：
2010-10-01
影响因子：
7.3
通讯作者：
Franchi, A. M.
中科院分区：
文献类型：
--
作者：
Cella, M.;Farina, M. G.;Franchi, A. M.
背景和疾病母体感染是不良发育结果的主要原因之一，包括胚胎吸收和早产。本研究建立了一种炎症相关性早产小鼠模型，并用于研究一氧化氮（NO）与前列腺素（PGs）的关系。一旦建立，其用于分析子宫内的野牡丹素E-2和F-2 α（通过放射免疫测定法）、环氧合酶（考克斯）和NOS蛋白（通过Western印迹法）的水平以及NO合酶（NOS）活性。研究了考克斯和NOS抑制剂对LPS诱导早产的影响。用一氧化氮供体（SNAP）进行体外试验，分析NO对前列腺素产生的调节作用。关键词脂多糖增加子宫NO和PG的合成，诱导早产。联合应用美洛昔康（一种环氧合酶-2抑制剂）或氨基胍（一种诱导型NOS抑制剂）可防止LPS诱导的早产，并阻断PG和NO的增加。低浓度的NO减少PG合成，而高浓度的NO增加PG合成。相关的早产模型表明，早产可以通过减少PG或NO的产生来预防。NO对PG的合成有双重作用，这取决于其浓度。这些数据有助于了解NO和PGs在妊娠和分娩中的相互作用，并有助于改善新生儿结局。
BACKGROUND AND PURPOSEMaternal infections are one of the main causes of adverse developmental outcomes including embryonic resorption and preterm labour. In this study a mouse model of inflammation-associated preterm delivery was developed, and used to study the relationship between nitric oxide (NO) and prostaglandins (PGs).EXPERIMENTAL APPROACHThe murine model of preterm labour was achieved by assaying different doses of bacterial lipopolysaccharides (LPS). Once established, it was used to analyse uterine levels of prostaglandins E-2 and F-2 alpha (by radioimmunoassay), cyclooxygenases (COX) and NOS proteins (by Western blot) and NO synthase (NOS) activity. Effects of inhibitors of COX and NOS on LPS-induced preterm labour were also studied. In vitro assays with a nitric oxide donor (SNAP) were performed to analyse the modulation of prostaglandin production by NO.KEY RESULTSLipopolysaccharide increased uterine NO and PG synthesis and induced preterm delivery. Co-administration of meloxicam, a cyclooxygenase-2 inhibitor, or aminoguanidine, an inducible NOS inhibitor, prevented LPS-induced preterm delivery and blocked the increase in PGs and NO. Notably, the levels of NO were found to determine its effect on PG synthesis; low concentrations of NO reduced PG synthesis whereas high concentrations augmented them.CONCLUSIONS AND IMPLICATIONSAn infection-associated model of preterm labour showed that preterm delivery can be prevented by decreasing PG or NO production. NO was found to have a dual effect on PG synthesis depending on its concentration. These data contribute to the understanding of the interaction between NO and PGs in pregnancy and parturition, and could help to improve neonatal outcomes.