Leptin does not influence surfactant synthesis in fetal sheep and mice lungs.
Leptin does not influence surfactant synthesis in fetal sheep and mice lungs.
复制标题
DOI：
10.1152/ajplung.00418.2010
复制
发表时间：
2011-03
期刊：
影响因子：
--
通讯作者：
A. Sato;Angelica Schehr;M. Ikegami
中科院分区：
文献类型：
--
作者：
A. Sato;Angelica Schehr;M. Ikegami
在胎儿体内，循环中的瘦素在妊娠晚期会增加，并可能影响胎儿器官的发育。先前利用胎儿肺外植体在体外已证实瘦素可增加表面活性物质。我们假设对胎羊和怀孕小鼠使用瘦素治疗可能会增加体内胎儿肺中表面活性物质的合成。在胎龄122 - 124天（足月为150天）时，在超声引导下给胎羊注射5毫克瘦素或安慰剂。注射3.5天后，早产羔羊娩出，在30分钟通气期间研究肺功能，随后分析肺表面活性物质成分。根据五种不同剂量、治疗次数和治疗胎龄的研究方案，给怀孕的A/J小鼠腹腔注射30毫克或300毫克瘦素或安慰剂。在母鼠最后一次治疗24小时后分析胎儿肺中的表面活性物质成分。给胎羊注射瘦素增加了胎儿体重。对照组和瘦素治疗组在肺功能（早产新生羔羊）、表面活性物质成分总量（羔羊和胎鼠）以及肺中与表面活性物质合成相关基因的表达（胎鼠）方面相似。同样，在所有年龄段，缺乏循环瘦素的小鼠（ob/ob小鼠）肺中的饱和磷脂酰胆碱和磷脂也是正常的。这些研究结果一致表明，无论是外源性给予瘦素还是瘦素缺乏都不会影响体内胎儿肺成熟或表面活性物质总量。此外，表面活性物质合成所必需的关键基因不受瘦素治疗的影响。
In the fetus, leptin in the circulation increases at late gestation and likely influences fetal organ development. Increased surfactant by leptin was previously demonstrated in vitro using fetal lung explant. We hypothesized that leptin treatment given to fetal sheep and pregnant mice might increase surfactant synthesis in the fetal lung in vivo. At 122-124 days gestational age (term: 150 days), fetal sheep were injected with 5 mg of leptin or vehicle using ultrasound guidance. Three and a half days after injection, preterm lambs were delivered, and lung function was studied during 30-min ventilation, followed by pulmonary surfactant components analyses. Pregnant A/J mice were given 30 or 300 mg of leptin or vehicle by intraperitoneal injection according to five study protocols with different doses, number of treatments, and gestational ages to treat. Surfactant components were analyzed in fetal lung 24 h after the last maternal treatment. Leptin injection given to fetal sheep increased fetal body weight. Control and leptin-treated groups were similar in lung function (preterm newborn lamb), surfactant components pool sizes (lamb and fetal mice), and expression of genes related to surfactant synthesis in the lung (fetal mice). Likewise, saturated phosphatidylcholine and phospholipid were normal in mice lungs with absence of circulating leptin (ob/ob mice) at all ages. These studies coincided in findings that neither exogenously given leptin nor deficiency of leptin influenced fetal lung maturation or surfactant pool sizes in vivo. Furthermore, the key genes critically required for surfactant synthesis were not affected by leptin treatment.