<b>Hepatic GPx1 and GIT1 Expression Altered by Ethanol Exposure During Third Trimester-Equivalent Development</b>

Ethanol (EtOH) exposure throughout gestation and breastfeeding periods leads to multiples adverse outcomes in the hepatic system. Under oxidative stress, alterations in liver are related to the inhibition of induced nitric oxide synthase activity in sinusoidal cells as a consequence of the G-protein-coupled receptor (GPCR)-kinase interacting (GIT1) low expression. Here, we hypothesized that both glutathione peroxidase 1 (GPx1) and GIT1 could be altered by EtOH exposure during the third trimester human equivalent development. Therefore, we ex-posed rats during the third trimester-equivalent [postnatal days (PD) 2-8] to moderate levels of maternal EtOH (20%). GPx1 and GIT1 expressions were detected by western blotting, antioxidant activity of GPx and concentration of hepatic carbonyl groups (PC) were determined by spectrophotometry. Serum biochemistry parameter, such as alanine aminotransferase (ALT), glucose (gluc), cholesterol (chol), and triglycerides (TG) were also measured. We found that ethanol de-creases both GIT1 and GPx1 selenoprotein expression, affecting the GPx antioxidant activity and conversely increasing the protein oxidation. These results demonstrate, for the first time that the GPx antioxidant system altered by EtOH exposure during the third trimester of development is related to a parallel decreased expression of the GIT1.在妊娠全程及母乳喂养阶段暴露于乙醇（Ethanol，EtOH），可对肝脏系统引发多种不良后果。在氧化应激条件下，肝组织的异常改变与窦状隙细胞中诱导型一氧化氮合酶活性受抑制密切相关，而该抑制效应源于G蛋白偶联受体（G-protein-coupled receptor，GPCR）激酶相互作用蛋白（GIT1）的低表达。本研究推测，在人类妊娠晚期等效发育阶段，乙醇暴露可同时改变谷胱甘肽过氧化物酶1（glutathione peroxidase 1，GPx1）与GIT1的表达水平。因此，本研究对处于人类妊娠晚期等效发育阶段[即出生后第2至8天（postnatal days，PD）2-8]的幼鼠施加20%浓度的母体乙醇暴露干预。采用蛋白质免疫印迹（western blotting）检测GPx1与GIT1的表达水平，通过分光光度法测定谷胱甘肽过氧化物酶的抗氧化活性以及肝羰基化合物（PC）的浓度；同时还检测了血清生化指标，包括丙氨酸氨基转移酶（alanine aminotransferase，ALT）、葡萄糖（glucose，缩写gluc）、胆固醇（cholesterol，缩写chol）以及甘油三酯（triglycerides，TG）。本研究发现，乙醇可同时降低GIT1与谷胱甘肽过氧化物酶1（GPx1）这两种硒蛋白的表达水平，进而削弱谷胱甘肽过氧化物酶的抗氧化活性，反之则会升高蛋白质氧化水平。本研究结果首次证实，发育阶段晚期乙醇暴露所改变的谷胱甘肽过氧化物酶抗氧化系统，与GIT1表达的同步下调存在显著相关性。