Lipopolysaccharide-induced chorioamnionitis and postnatal lung injury: The beneficial effects of L-citrulline in newborn rats
Lipopolysaccharide-induced chorioamnionitis and postnatal lung injury: The beneficial effects of L-citrulline in newborn rats
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DOI：
10.1080/01902148.2018.1497730
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发表时间：
2018-01-01
影响因子：
1.7
通讯作者：
Zaramella, Patrizia
中科院分区：
文献类型：
--
作者：
Dedja, Arben;Gucciardi, Antonina;Zaramella, Patrizia
研究目的：新生儿的肺结构似乎受到母体绒毛膜蜕膜层感染的炎症反应的影响。将L-瓜氨酸（L-Cit）给予暴露于羊膜内脂多糖（LPS）诱导的绒毛膜炎的妊娠大鼠，以研究其对新生儿肺损伤的影响。材料与方法：将幼仔分配到四个实验组：1-幼仔暴露于羊膜内NaCl但不暴露于出生后L-Cit（对照）; 2 -幼仔暴露于羊膜内NaCl以及出生后L-Cit处理（L-Cit组）; 3 -幼仔暴露于产前LPS但不暴露于出生后（LPS）; 4-幼仔暴露于产前LPS以及出生后L-Cit处理（LPS + L-Cit）。每组中的一些幼仔在出生后（P）第3天处死，其他在第7天处死。收获幼仔的肺用于形态测定分析;定量细胞因子、谷胱甘肽酶1和VEGF值。血清精氨酸，瓜氨酸，不对称二甲基精氨酸（ADMA），对称二甲基精氨酸，N-G-单甲基精氨酸，和高精氨酸水平测定使用UPLC-MS/MS。结果：L-Cit衰减LPS+ L-Cit组肺泡生长的破坏。精氨酸、高精氨酸和ADMA水平在LPS处理组中下降。精氨酸和ADMA在L-Cit组中在P7时升高，其成员相对于对照也显示出更高的VEGF水平。相反，对照组在P7时显示出比L-Cit组更高的IL-10和IL-1/β值。在P7，LPS组中精氨酸酶1相对于对照更高。结论：L-Cit可促进新生大鼠肺泡和血管的生长，减轻羊膜内LPS暴露后的肺部炎症反应。ADMA/DDAH/NO通路似乎可以抵消促炎性细胞因子的产生并维持巨噬细胞的迁移。
Aim of the study: The lung architecture of newborns appears to be affected by an inflammatory reaction to maternal choriodecidual layer infection. L-citrulline (L-Cit) was administered to pregnant rats exposed to intra-amniotic lipopolysaccharide (LPS)-induced chorioamnionitis to investigate its effect on neonatal lung injury. Materials and Methods: The pups were assigned to four experimental groups: 1- pups exposed to intra-amniotic NaCI but not to postnatal L-Cit (Controls); 2 - pups exposed to intra-amniotic NaCl as well as to postnatal L-Cit treatment (L-Cit group); 3 - pups exposed to prenatal LPS but not to postnatal (LPS); 4- pups exposed to prenatal LPS as well as to postnatal L-Cit treatment (LPS + L-Cit). Some pups in each group were sacrificed on postnatal (P) day 3 and others on day 7. The pups' lungs were harvested for morphometric analysis; cytokine, arginase 1, and VEGF values were quantified. Serum arginine, citrulline, asymmetric dimethylarginine (ADMA), symmetric dimethylarginine, N-G-monomethyl arginine, and homoarginine levels were determined using UPLC-MS/MS. Results: L-Cit attenuated the disruption of alveolar growth in the LPS+ L-Cit group. Arginine, homo-arginine, and ADMA levels fell in the LPS treated groups. Arginine and ADMA rose at P7 in the L-Cit group whose members also showed higher VEGF levels with respect to the Controls. The Controls, instead, showed higher IL-10 and IL-1/beta values with respect to the L-Cit group at P7. Arginase 1 was higher in the LPS groups with respect to the Controls at P7. Conclusions: L-Cit improved alveolar and vascular growth diminishing the lung inflammatory response in the newborn rats exposed to intra-amniotic LPS. The ADMA/DDAH/NO pathway appeared to counteract proinflam-matory cytokine production and to sustain macrophage migration.