锌过载抑制仔猪肠道能量代谢的机制研究

断奶仔猪的肠道功能尚不成熟，日粮中过量锌易造成仔猪肠道损伤。前期研究发现能量代谢受损可能是锌过载造成细胞死亡的主要原因，而锌过载造成能量损伤的机制尚不明确。本项目在前期研究基础上，以断奶仔猪及其空肠上皮细胞为对象，拟通过动物在体试验和构建细胞单层模型，研究过量锌对肠道的损伤效应，并从糖酵解和三羧酸循环路径研究锌对能量代谢的抑制状况；以猪空肠上皮细胞为模型，通过能量代谢底物补偿探讨能量代谢抑制在锌过载损伤中的主导效应；通过抑制胞内活性氧、氮自由基生成，明确锌过载造成的氧化应激与能量损伤之间的关系；通过基因敲除及脂质体转染，进一步明确高浓度锌诱导肠道能量损伤的途径。通过上述研究，揭示锌过载抑制仔猪肠道能量代谢的可能机制与通路，为畜牧生产科学应用锌元素提供理论依据。

Intestinal functions in piglets are not well developed after weaning, excessive zinc in feed can interact with intestine directly and cause intestinal damage on piglets. Previous studies have shown that energy depletion may play a major role in zinc overload-induced cell death, while the mechanism of energy depletion caused by excessive zinc is still unclear. With the aim of clarifying the precise mechanism of zinc overload-induced energy depletion and then laying foundation for the scientific application of zinc, a series of related experiments are designed in the present project. Piglets and porcine jejunum epithelial cells (IPEC-J2) monolayer will be used to study the effects of zinc overload on intestinal damage. Glycolysis and tricarboxylic acid cycle pathways will be evaluated to study the effects of excessive zinc on energy depletion. Supplementing energy metabolism substrates will also be used in vitro to investigate the dominant effect of energy depletion in zinc overload-induced cell death. Furthermore, ROS and RNS inhibition will be conducted to clarify the relationship between oxidative stress and energy depletion induced by excessive zinc. Lipofection and PARP-1 knockout will be performed to reveal the possible pathway of zinc overload-induced energy depletion.