Prevention of fetal demise and growth restriction in a mouse model of fetal alcohol syndrome.
Prevention of fetal demise and growth restriction in a mouse model of fetal alcohol syndrome.
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发表时间：
2001-05
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通讯作者：
C. Spong;D. Abebe;I. Gozes;D. Brenneman;Joannam . Hill
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作者：
C. Spong;D. Abebe;I. Gozes;D. Brenneman;Joannam . Hill
两种肽 [NAPVSIPQ (NAP) 和 SALLRSIPA (ADNF-9)] 与血管活性肠肽调节的新型神经胶质蛋白相关，现在已被证明可以在胎儿酒精综合症模型中提供保护性干预。在妊娠中期（E8）向怀孕小鼠腹腔注射乙醇后，产生胎儿死亡和生长受限。据信，发育过程中酒精治疗引起的死亡和生长异常在一定程度上与严重的氧化损伤有关。 NAP 和 ADNF-9 已被证明在体外具有抗氧化和抗凋亡作用。用等摩尔肽组合进行预处理可防止酒精引起的胎儿死亡和生长异常。单独使用 NAP 进行预处理可显着减少与酒精相关的胎儿死亡；而单独使用 ADNF-9 对酒精暴露后胎儿的存活没有可检测到的影响，这表明这些肽之间存在药理学差异。对胎儿的生化评估表明，组合肽治疗可防止酒精引起的还原型谷胱甘肽减少。无论是预处理 30 分钟还是酒精给药后 1 小时，肽功效都很明显。 [(3)H]NAPVSIPQ 的生物利用度研究表明，给药 60 分钟后，39% 的总放射性与胎儿中的完整肽发生共迁移。这些研究表明，组合肽治疗可以预防与产前酒精暴露相关的胎儿死亡和生长受限，并建议在与氧化应激相关的其他模型/疾病中探索这种治疗策略。
Two peptides [NAPVSIPQ (NAP) and SALLRSIPA (ADNF-9)], that are associated with novel glial proteins regulated by vasoactive intestinal peptide, are shown now to provide protective intervention in a model of fetal alcohol syndrome. Fetal demise and growth restrictions were produced after intraperitoneal injection of ethanol to pregnant mice during midgestation (E8). Death and growth abnormalities elicited by alcohol treatment during development are believed to be associated, in part, with severe oxidative damage. NAP and ADNF-9 have been shown to exhibit antioxidative and antiapoptotic actions in vitro. Pretreatment with an equimolar combination of the peptides prevented the alcohol-induced fetal death and growth abnormalities. Pretreatment with NAP alone resulted in a significant decrease in alcohol-associated fetal death; whereas ADNF-9 alone had no detectable effect on fetal survival after alcohol exposure, indicating a pharmacological distinction between the peptides. Biochemical assessment of the fetuses indicated that the combination peptide treatment prevented the alcohol-induced decreases in reduced glutathione. Peptide efficacy was evident with either 30-min pretreatment or with 1-h post-alcohol administration. Bioavailability studies with [(3)H]NAPVSIPQ indicated that 39% of the total radioactivity comigrated with intact peptide in the fetus 60 min after administration. These studies demonstrate that fetal death and growth restriction associated with prenatal alcohol exposure were prevented by combinatorial peptide treatment and suggest that this therapeutic strategy be explored in other models/diseases associated with oxidative stress.