Bai Kaiwen, Jiang Luyi, Wei Chengheng, Li Qiming, Zhang Lili, Zhang Jingfei, Wang Tian
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, China.
College of Animal Science, Zhejiang University, Hangzhou, Zhejiang, 310000, China.
Free Radic Biol Med. 2022 May 1;184:89-98. doi: 10.1016/j.freeradbiomed.2022.04.004. Epub 2022 Apr 9.
The objectives of this study were focused on the mechanism of mitochondrial dysfunction in skeletal muscle stem cells (MuSCs) from intrauterine growth restriction (IUGR) newborn piglets, and the relief of dimethylglycine sodium salt (DMG-Na) on MuSCs mitochondrial dysfunction by Nrf2/SIRT1/PGC1α network. In this study, six newborn piglets with normal birth weight (NBW) and six IUGR newborn piglets were slaughtered immediately after birth to obtain longissimus dorsi muscle (LM) samples. MuSCs were collected and divided into three groups: MuSCs from NBW newborn piglets (N), MuSCs from IUGR newborn piglets (I), and MuSCs from IUGR newborn piglets with 32 μmol DMG-Na (ID). Compared with the NBW group, the IUGR group showed decreased (P < 0.05) serum and LM antioxidant defense capacity, and increased (P < 0.05) serum and LM damage. Compared with the N group, the I group showed decreased (P < 0.05) MuSCs antioxidant defense capacity, mitochondrial ETC complexes, energy metabolites, and antioxidant defense-related and mitochondrial function-related gene and protein expression levels. The antioxidant defense capacity, mitochondrial ETC complexes, energy metabolites, and antioxidant defense-related and mitochondrial function-related gene and protein expression levels of MuSCs were improved (P < 0.05) in the ID group compared to those in the I group. The MuSCs of IUGR newborns activate the Nrf2/SIRT1/PGC1α network by taking in DMG-Na, thereby neutralizing excessive generated O that may help to improve their unfavorable mitochondrial dysfunction in skeletal muscle.
本研究的目的集中于宫内生长受限（IUGR）新生仔猪骨骼肌干细胞（MuSCs）中线粒体功能障碍的机制，以及二甲基甘氨酸钠盐（DMG-Na）通过Nrf2/SIRT1/PGC1α网络对MuSCs线粒体功能障碍的缓解作用。在本研究中，六只出生体重正常（NBW）的新生仔猪和六只IUGR新生仔猪在出生后立即屠宰，以获取背最长肌（LM）样本。收集MuSCs并分为三组：来自NBW新生仔猪的MuSCs（N）、来自IUGR新生仔猪的MuSCs（I）以及来自接受32 μmol DMG-Na处理的IUGR新生仔猪的MuSCs（ID）。与NBW组相比，IUGR组血清和LM的抗氧化防御能力降低（P < 0.05），血清和LM损伤增加（P < 0.05）。与N组相比，I组MuSCs的抗氧化防御能力、线粒体电子传递链复合物、能量代谢产物以及与抗氧化防御和线粒体功能相关的基因和蛋白质表达水平降低（P < 0.05）。与I组相比，ID组MuSCs的抗氧化防御能力、线粒体电子传递链复合物、能量代谢产物以及与抗氧化防御和线粒体功能相关的基因和蛋白质表达水平得到改善（P < 0.05）。IUGR新生仔猪的MuSCs通过摄取DMG-Na激活Nrf2/SIRT1/PGC1α网络，从而中和过量产生的O，这可能有助于改善其骨骼肌中不利的线粒体功能障碍。
