Attenuation of lipopolysaccharide-induced inflammatory response and phospholipids metabolism at the feto-maternal interface by N-acetyl cysteine.
Attenuation of lipopolysaccharide-induced inflammatory response and phospholipids metabolism at the feto-maternal interface by N-acetyl cysteine.
复制标题
DOI：
10.1203/pdr.0b013e318181e07c
复制
发表时间：
2008-10
影响因子：
3.6
通讯作者：
Singh I
中科院分区：
文献类型：
--
作者：
Paintlia MK;Paintlia AS;Singh AK;Singh I
母体微生物感染导致不良的胎儿发育结果，包括胚胎吸收、宫内胎儿死亡和早产。近年来的研究表明，氧化应激在脉络膜炎的发病机制中起重要作用。本研究探讨了N-乙酰半胱氨酸（NAC）对脂多糖诱导的小鼠早产和胎儿死亡的影响。在胚胎第18天暴露于脂多糖表明妊娠母鼠流产率和胎儿死亡率增加。这与炎症反应（细胞因子、趋化因子和iNOS表达）增加和胎盘中白细胞（单核细胞和多形核细胞）浸润有关。胎盘中胞浆和分泌型磷脂酶A2的表达增加，前列腺素-2和白三烯B4的分泌增加，提示磷脂代谢增加。此外，胎盘中环氧合酶-2和丙二醛（氧化应激标志物）的表达增加。相反，NAC预处理消除了胎盘中脂多糖的这些作用。总的来说，这些数据提供的证据表明，LPS诱导的炎症增加和磷脂在胎儿-母体界面（胎盘）的代谢对于母体微生物感染期间的早产和胎儿死亡至关重要，这可以通过基于抗氧化剂的治疗来阻断。
Maternal microbial infections cause adverse fetal developmental outcomes including embryonic resorption, intrauterine fetal death, and preterm labor. Recent studies demonstrated that oxidative-stress plays an important role in chorioamniotitis pathogenesis. Herein we investigated the effect of N-acetyl cysteine (NAC) on lipopolysaccharide-induced preterm labor and fetal demise in murine model. Lipopolysaccharide exposure at embryonic day 18 demonstrated an increase in the abortion rate and fetal demise in pregnant dams. This was associated with increase in an inflammatory response (cytokines, chemokines and iNOS expression) and infiltration of leukocytes (monocytes and polymorphonuclear cells) in the placenta. There was increased expression of cytosolic and secretary phospholipase A2 with increased secretion of prostaglandin-2 and leukotriene B4 in the placenta, suggestive of increased metabolism of phospholipids. In addition, expression of cycloxygenase-2 and malondialdehyde production (oxidative-stress marker) was increased in the placenta. Conversely, NAC pretreatment abolished these effects of lipopolysaccharide in the placenta. Collectively, these data provide evidence that LPS-induced increased inflammation and metabolism of phospholipids at the feto-maternal interface (placenta) is critical for preterm labor and fetal demise during maternal microbial infections which could be blocked by antioxidant-based therapies.