围产期能量负平衡奶牛的内质网应激不仅影响乳腺上皮细胞的分化与凋亡，还会降低奶牛泌乳性能，给奶牛业造成了严重的经济损失，因此开展围产期奶牛内质网应激发生及调控机制的研究尤为迫切。申请人前期研究发现UFL1基因可以有效调缓解奶牛乳腺上皮细胞炎性损伤，并在内质网应激中发挥调控作用，但其调节内质网应激的分子机制尚不清楚。为此，本项目以围产期荷斯坦奶牛为研究对象，结合围产期奶牛高NEFA血症的代谢特征，首先开展体内实验，明确NEFA诱导奶牛乳腺内质网应激的发生机制及其对泌乳性能的影响；然后体外以奶牛乳腺上皮细胞为研究对象，开展UFL1在NEFA诱导的乳腺上皮细胞内质网应激中的作用与机制研究，旨在阐明围产期奶牛内质网应激的发生及调控机制，为促进围产期奶牛抗病育种研究、提高奶牛生产性能提供新思路。

Endoplasmic reticulum stress in mammary gland of transition dairy cows with high level of negative energy balance affects the differentiation and apoptosis of bovine mammary epithelial cells (BMECs), as well as milk yield, which seriously hinders the healthy development of dairy industry. Therefore, studies of the mechanisms driving and regulating ER stress in transition dairy cows are urgent. In the previous study, we have found that UFL1 could alleviate LPS-induced cell damage and regulate ER stress in BMECs, but the molecular mechanism of UFL1 in regulating ER stress remains unclear. Thus, the objective of this project is to study the role of UFL1 in NEFA induced-ER stress both in vivo and vitro. Firstly, we will evaluate the effect of NEFA on ER stress and lactation performance in transition dairy cows; Then, we will study roles of UFL1 in NEFA-induced ER stress in BMECs in order to provide a theoretical basis for solving the problems of lactation and negative energy balance in transition dairy cows.