N-氨甲酰谷氨酸对宫内发育迟缓哺乳羔羊肠道线粒体自噬的调控机制

Previous studies have shown that the intestinal reactive oxygen species (ROS) level was increased by intrauterine growth retardation (IUGR), which results to oxidative stress, and will further induce intestinal mitochondrial autophagy. N‑carbamylglutamate (NCG) has an antioxidant function. However, the effect of IUGR on intestinal mitochondrial autophagy in lambs and the regulatory mechanism for IUGR lambs is rarely reported. In vivo experiment, this study will clarify the effects of NCG on the intestinal mitochondrial structure, function and the PINK1/Parkin pathway mediated by ROS. In vitro experiment, H2O2 was used to establish the oxidative stress of ovine intestinal cells and induce the occurrence of mitochondrial autophagy. ROS scavenger and mitochondrial autophagy inhibitor were used to demonstrate the positive and negative effects of ROS in the PINK1/Parkin pathway and mitochondrial autophagy, and furthermore to clarify the mechanism of PINK1/Parkin pathway in NCG regulating intestinal epithelial mitochondrial autophagy. These studies will reveal the regulation mechanism of NCG on the intestinal mitochondrial autophagy of IUGR suckling lambs. These studies will also provide a scientific basis for the optimal preparation of NCG in lamb milk replacer, the improvement of NCG on the injury of intestinal mitochondrial structure and function, and the growth in IUGR suckling lambs.

宫内发育迟缓（IUGR）诱发肠道活性氧（ROS）含量升高，导致氧化应激反应，继而将诱导肠道线粒体自噬的发生。N-氨甲酰谷氨酸（NCG）具有抗氧化功能。然而，IUGR对哺乳羔羊肠道线粒体自噬的影响及对其调控机制鲜见报道。首先，本研究将通过体内试验阐明NCG对IUGR羔羊肠道线粒体结构、功能和ROS介导的线粒体自噬PINK1/Parkin途径及其自噬发生标记分子的调控机制。而后，采用H2O2建立羊肠道细胞氧化应激反应，诱导肠黏膜线粒体自噬发生，并通过使用ROS清除剂和线粒体自噬抑制剂，从正、反两方面论证ROS在PINK1/Parkin途径以及线粒体自噬中的作用，阐明该途径在NCG调控肠上皮细胞线粒体自噬中的作用机制。通过以上研究将揭示NCG对IUGR哺乳羔羊肠道线粒体自噬的调控机制，为NCG在羔羊代乳粉的优化配制，修复IUGR哺乳羔羊肠道线粒体结构和功能损伤，最终促进其生长发育提供科学依据。

在我国养羊生产中因营养供给缺乏或管理不当，常导致母羊在妊娠期胚胎营养供给不足，进而引起宫内发育迟缓（IUGR）。IUGR诱发了肠道活性氧（ROS）含量升高，导致氧化应激反应，继而将诱导肠道线粒体自噬的发生。N-氨甲酰谷氨酸（NCG）具有抗氧化功能。然而，IUGR对哺乳羔羊肠道线粒体自噬的影响及对其调控机制鲜见报道。为探明NCG对IUGR哺乳羔羊肠道线粒体自噬调控的机制，该项目通过体内试验阐明了NCG对IUGR羔羊肠道线粒体结构、功能和ROS介导的线粒体自噬PINK1/Parkin途径的调控机制。采用H2O2建立了羊肠道细胞氧化应激反应，诱导了肠黏膜线粒体自噬发生，并通过使用ROS清除剂和线粒体自噬抑制剂，论证了ROS在PINK1/Parkin途径以及线粒体自噬中的作用，阐明了该途径在NCG调控肠上皮细胞线粒体自噬中的作用机制。该研究结果为NCG修复IUGR哺乳羔羊肠道线粒体结构和功能损伤，促进其生长发育提供了科学依据。