N-acetylcysteine attenuates intrauterine growth retardation-induced hepatic damage in suckling piglets by improving glutathione synthesis and cellular homeostasis
N-acetylcysteine attenuates intrauterine growth retardation-induced hepatic damage in suckling piglets by improving glutathione synthesis and cellular homeostasis
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DOI：
10.1007/s00394-016-1322-x
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发表时间：
2018-02
影响因子：
5
通讯作者：
Hao Zhang;W. Su;Z. Ying;Yueping Chen;Le Zhou;Yue Li;Jingfei Zhang;Lili Zhang;Tian Wang
中科院分区：
文献类型：
--
作者：
Hao Zhang;W. Su;Z. Ying;Yueping Chen;Le Zhou;Yue Li;Jingfei Zhang;Lili Zhang;Tian Wang
目的探讨N-乙酰半胱氨酸（NAC）对宫内生长迟缓（IUGR）仔猪肝损伤的保护作用。仔猪出生后7日龄断奶，饲喂对照配方乳（NBW-CON组和IUGR-CON组）或添加NAC 1.2g/kg的对照配方乳（IUGR-NAC组）14 d（n= 7）。结果与NBW-CON组相比，IUGR-CON组血浆转氨酶活性升高，肝细胞凋亡数增多，蛋白质羰基、丙二醛（MDA）、微管相关蛋白1轻链3 β、和磷脂缀合形式（MAP 1 LC 3B-II），沿着还原型谷胱甘肽（GSH）含量的降低。NAC处理增加了IUGR-NAC组肝脏中GSH含量和GSH与氧化型GSH的比值，可能是由于γ-谷氨酰胺-半胱氨酸连接酶、γ-谷氨酰胺-半胱氨酸合成酶和谷胱甘肽还原酶活性的提高。与IUGR CON组相比，IUGR NAC组肝组织蛋白质羰基化和MDA含量降低。此外，NAC处理的仔猪有一个增加的B细胞淋巴瘤/白血病2蛋白的含量，而MAP 1 LC 3 B-II在liver.ConclusionsNAC的表达水平下降可能有有益的影响，在改善GSH合成和细胞内稳态的IUGR哺乳仔猪的肝脏。
PurposeThe objective of the present study was to test the hypothesis thatN-acetylcysteine (NAC) may play beneficial roles against intrauterine growth retardation (IUGR)-induced hepatic damage in suckling piglets.MethodsFourteen IUGR and seven normal birth weight (NBW) neonatal male piglets were selected. Piglets were weaned at 7 days of postnatal age and fed the control formula milk (NBW-CON and IUGR-CON groups) or the control formula milk supplemented with 1.2 g/kg NAC (IUGR-NAC group) for 14 days (n= 7). The plasma and liver samples were analyzed for the parameters related to hepatic damage, redox status, apoptosis, and autophagy.ResultsCompared with the NBW-CON group, IUGR-CON group exhibited increased activities of plasma aminotransferases, increased numbers of apoptotic hepatocytes, as well as higher concentrations of protein carbonyl, malondialdehyde (MDA), microtubule-associated protein 1 light chain 3 beta, and phospholipid-conjugated form (MAP1LC3B-II), along with a decrease in the content of reduced glutathione (GSH). NAC treatment increased GSH content and GSH-to-oxidized GSH ratio in the liver of IUGR-NAC group, most likely owing to the improved activities of γ-glutamine-cysteine ligase, γ-glutamine-cysteine synthetase, and glutathione reductase. The hepatic protein carbonyl and MDA contents were decreased in the IUGR-NAC group compared with the IUGR-CON group. In addition, NAC-treated piglets had an increased content of B cell lymphoma/leukemia 2 protein, whereas a decreased expression level of MAP1LC3B-II in the liver.ConclusionsNAC may have beneficial effects in improving GSH synthesis and cellular homeostasis in the liver of IUGR suckling piglets.