Hepatocyte necroptosis is associated with liver damage in dairy cows with ketosis

作者：Menglin Liu, Jingmin Gu, Chenchen Zhao, Jinxia Li, Fanrong Kong, Xinyu Du, Dandan Qi, Enzhu Li, Jie Gao, Xiliang Du, Yuxiang Song, Guowen Liu, Wenwen Gao, Xinwei Li, Lin Lei · 发表于：Journal of Dairy Science · 年份：2025 · DOI：10.3168/jds.2025-26349 · 被引用次数：4 · 研究领域：Liver Disease Diagnosis and Treatment、Lipid metabolism and disorders、Diet, Metabolism, and Disease

Dairy cows with ketosis frequently exhibit impaired liver function and inflammation. Necroptosis, a form of programmed cell death associated with cellular lysis, releases damage-associated molecular patterns (DAMP) into injured tissues, thereby amplifying inflammatory responses and tissue damage. However, the role of necroptosis in the liver of ketotic cows remains unknown. The present study aimed to investigate whether necroptosis is associated with hepatic damage in dairy cows with ketosis. Dairy cows were selected as either the clinically healthy control group (n = 15) or a ketotic group diagnosed with ketosis, and were matched for lactation numbers (median = 3, range = 2-4) and DIM (median = 6 d, range = 3-9 d). Liver tissue samples were collected via percutaneous needle biopsy, and blood samples were obtained by coccygeal venipuncture. Primary bovine hepatocytes were isolated from the liver of 1-d-old calves. In vivo experiments showed significant increases in the activity of alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl-transferase (GGT), and glutamate dehydrogenase (GLDH) in the blood of ketotic cows. Concurrently, the mRNA abundance of IL-6 (IL6), tumor necrosis factor-α (TNF), and IL-1β (IL1B) in the liver of ketotic cows also significantly increased. Histopathological examination revealed significant cytoplasmic vacuolation, lytic necrosis, and inflammatory cell infiltration in the liver of ketotic cows, along with increased CD11b ...