Journal of agricultural and food chemistry · 2025
Nrf2 Promotes BHBA-Induced Pyroptosis in Bovine Endometrial Epithelial Cells by Modulating Autophagy Mediated through Oxidative Stress.
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Mu Jiajia, Sun Qiannan, Lin Nanyan, Ishrat Khan, Tian Tian, Yue Chenguang, Tong Xishuai, Zhu Jiaqiao, Zou Hui, Zhao Hongyan, Song Ruilong, Gu Jianhong, Yuan Yan, Bian Jianchun, Liu Zongping, Ma Yonggang
Аннотация
Ketotic cows exhibit a heightened secondary endometritis risk through an unknown mechanism. We investigated the role of Nrf2 in ketosis-induced endometritis. Uterine tissues from ketotic cows showed higher levels of caspase-1 and GSDMD but lower levels of Nrf2 and LC3. β-Hydroxybutyrate (BHBA) treatment induced pyroptosis in bovine endometrial epithelial cells (BEECs), upregulated pyroptosis-related proteins, and increased the rate of pyroptosis. Nrf2 and its downstream oxidative stress proteins were decreased, and autophagic flux was blocked. NAC, Rapa, and Nrf2 activators alleviated BHBA-induced pyroptosis by promoting autophagic flux. In a mouse ketosis model, intervention with NAC significantly reduced blood levels of BHBA and pro-inflammatory cytokines, and the expression of pyroptosis-related proteins in uterine tissues was decreased compared with ketotic model mice. Overall, Nrf2 promoted BHBA-induced pyroptosis in BEECs by modulating autophagy mediated by oxidative stress, suggesting that it may serve as a potential therapeutic target.