Heilongjiang Provincial Key Laboratory of Prevention and Control of Bovine Diseases, College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing, Heilongjiang Province 163319, China.
Mammalian NutriPhysioGenomics, Department of Animal Sciences and Division of Nutritional Sciences, University of Illinois, Urbana 61801.
J Dairy Sci. 2021 Jan;104(1):849-861. doi: 10.3168/jds.2020-18788. Epub 2020 Oct 31.
Ketosis is a serious metabolic disorder characterized by systemic and hepatic oxidative stress, inflammation, and apoptosis, as well as reduced milk yield. Because of the paucity of data on mammary responses during ketosis, the aim of this study was to evaluate alterations in oxidative stress, NF-κB signaling, NLRP3 inflammasome, and caspase apoptotic pathways in mammary gland of dairy cows with ketosis. Blood, mammary gland tissue, and milk samples were collected from healthy cows [Control, blood concentration of β-hydroxybutyrate (BHB) <0.6 mM, n = 10] and cows with subclinical ketosis (SCK, blood concentration of BHB >1.2 mM and <3 mM, n = 10) or clinical ketosis (CK, blood concentration of BHB >3 mM, n = 10) at median 8 d in milk (range = 6-12). Compared with Control, serum concentration of glucose was lower (3.91 vs. 2.86 or 2.12 mM) in cows with SCK or CK, whereas concentrations of fatty acids (0.25 vs. 0.57 or 1.09 mM) and BHB (0.42 vs. 1.81 or 3.85 mM) were greater. Compared with Control, the percentage of milk fat was greater in cows with SCK or CK. In contrast, the percentage of milk protein was lower in cows with SCK or CK. We detected no differences in milk lactose content across groups. Compared with Control, activities of glutathione peroxidase, superoxide dismutase, and catalase were lower in mammary gland tissue of cows with SCK or CK. In contrast, concentrations of hydrogen peroxide and malondialdehyde were greater in cows with SCK or CK. Compared with Control, mRNA abundances of TNFA, IL6, and IL1B were greater in mammary tissues of cows with SCK or CK. In addition, activity of IKKβ and the ratio of phosphorylated inhibitor of κBα to IκBα, and of phosphorylated NF-κB p65 to NF-κB p65, were also greater in mammary tissues of cows with SCK or CK. Subclinical or clinical ketosis also led to greater activity of caspase 1 and protein abundance of caspase 1, NLRP3, Bax, caspase 3, and caspase 9. In contrast, abundance of the antiapoptotic protein was lower in SCK or CK cows. The data indicate that the mammary gland of SKC or CK cows undergoes severe oxidative stress, inflammation, and cell death.
酮症是一种严重的代谢紊乱，其特征是全身和肝脏的氧化应激、炎症和细胞凋亡，以及产奶量减少。由于酮症期间乳腺反应的数据匮乏，本研究旨在评估奶牛酮症时乳腺的氧化应激、NF-κB 信号通路、NLRP3 炎性小体和细胞凋亡途径的变化。从健康奶牛（对照组，血液中β-羟丁酸（BHB）浓度<0.6 mM，n=10）和亚临床酮症（SCK，血液中 BHB 浓度>1.2 mM 且<3 mM，n=10）或临床酮症（CK，血液中 BHB 浓度>3 mM，n=10）奶牛中采集血液、乳腺组织和牛奶样本，中位产奶期为 8 天（范围为 6-12 天）。与对照组相比，SCK 或 CK 奶牛的血清葡萄糖浓度较低（3.91 与 2.86 或 2.12 mM），而脂肪酸（0.25 与 0.57 或 1.09 mM）和 BHB（0.42 与 1.81 或 3.85 mM）浓度较高。与对照组相比，SCK 或 CK 奶牛的乳脂百分比更高。相反，SCK 或 CK 奶牛的乳蛋白百分比较低。各组间牛奶乳糖含量无差异。与对照组相比，SCK 或 CK 奶牛的乳腺组织中谷胱甘肽过氧化物酶、超氧化物歧化酶和过氧化氢酶的活性较低。相反，SCK 或 CK 奶牛的过氧化氢和丙二醛浓度较高。与对照组相比，SCK 或 CK 奶牛的乳腺组织中 TNFA、IL6 和 IL1B 的 mRNA 丰度较高。此外，SCK 或 CK 奶牛的 IKKβ 活性以及磷酸化 IκBα/IKKβ和磷酸化 NF-κB p65/NF-κB p65 的比值也较高。亚临床或临床酮症还导致 caspase 1 活性和 caspase 1、NLRP3、Bax、caspase 3 和 caspase 9 的蛋白丰度增加。相反，SCK 或 CK 奶牛的抗凋亡蛋白丰度较低。数据表明，SKC 或 CK 奶牛的乳腺经历了严重的氧化应激、炎症和细胞死亡。
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