Keap1-Nrf2/ARE信号通路及其在畜禽抗氧化中的研究进展

正常生理状态下，动物体内自由基的产生和清除处于稳定的动态平衡，但发生氧化应激时，体内自由基产生的量超过自身清除能力，引起氧化系统和抗氧化系统的失衡，造成氧化损伤。而Keap1-Nrf2/ARE信号通路的激活在预防氧化应激引起的细胞和组织损伤、维持氧化还原平衡和蛋白质稳态以及调节炎症方面具有关键作用。Keap1是Nrf2的胞浆抑制蛋白，在正常生理状态下，Nrf2与Keap1结合而发生泛素化和蛋白酶体降解，使细胞核内Nrf2的含量维持在一个相对较低的水平。在氧化应激条件下，Keap1对Nrf2的泛素化和降解的能力减弱，细胞核中Nrf2积聚，Nrf2与抗氧化反应元件（ARE）结合后启动下游一系列保护性基因的表达，使机体从氧化应激状态恢复到正常的生理状态。氧化应激参与多种病理生理变化，对畜禽的生产性能、生长发育、繁殖性能、肉品质等有负面影响，Keap1-Nrf2/ARE信号通路是细胞内最重要的抗氧化应激通路之一，对动物的健康保护极其重要。作者总结了Keap1-Nrf2/ARE信号通路的基本结构和活化机制及其在畜禽抗氧化中的研究进展，阐述了其在提高畜禽的抗氧化、抗炎能力和在肉品质中的重要作用，以期为缓解当前畜禽业中严重的氧化应激和炎症提供理论依据。

The Reasearch Progress of Keap1-Nrf2/ARE Signaling Pathway and Its Role in the Antioxidation of Livestock and Poultry

Under normal physiological conditions,the generation and scavenging of free radicals in animals are in a stable dynamic balance.However,when oxidative stress occurs,the amount of free radicals in the body exceeds the scavenging capacity,causing the imbalance between the oxidation system and the antioxidant system and causing oxidative damage.Activation of the Keap1-Nrf2/ARE signaling pathway plays a key role in preventing cellular and tissue damage caused by oxidative stress,maintaining redox balance and protein homeostasis,and regulating inflammation.Keap1 is a cytoplasmic inhibitor of Nrf2.Under normal physiological conditions,Nrf2 binds to its inhibitor Keap1 to undergo ubiquitination and proteasomal degradation,maintaining the Nrf2 content in the nucleus at a relatively low level.Under oxidative stress,the ability of Keap1 to ubiquitinate and degrade Nrf2 is weakened,Nrf2 accumulates in the nucleus,and Nrf2 binds to the antioxidant response element (ARE) to initiate the expression of a series of downstream protective genes,which makes the body returns to a normal physiological state from oxidative stress.Oxidative stress is involved in a variety of pathophysiological changes,which have a negative impact on livestock production performance,growth and development,reproductive performance,meat quality,etc.Keap1-Nrf2/ARE signaling pathway is one of the most important antioxidant stress pathways in cells,so it is extremely important to the health protection of animals.The authors summarizes the basic structure and activation mechanism of Keap1-Nrf2/ARE signaling pathway and the research progress in livestock and poultry,and describes its important role in improving the antioxidant,anti-inflammatory and meat quality of livestock and poultry,in order to provide a theoretical basis for solving the serious oxidative stress and inflammation in the current livestock industry.