College of Veterinary Medicine, Jilin University, Changchun 130062, China.
College of Animal Science and Veterinary Medicine, Heilongjiang Bayi Agricultural University, Daqing 163000, China.
Int J Mol Sci. 2020 May 8;21(9):3321. doi: 10.3390/ijms21093321.
Mastitis is one of three bovine diseases recognized as a cause of substantial economic losses every year throughout the world. Niacin is an important feed additive that is used extensively for dairy cow nutrition. However, the mechanism by which niacin acts on mastitis is not clear. The aim of this study is to investigate the mechanism of niacin in alleviating the inflammatory response of mammary epithelial cells and in anti-mastitis. Mammary glands, milk, and blood samples were collected from mastitis cows not treated with niacin ( = 3) and treated with niacin (30 g/d, = 3) and healthy cows ( = 3). The expression of GPR109A, IL-6, IL-1β, and TNF-α in the mammary glands of the dairy cows with mastitis was significantly higher than it was in the glands of the healthy dairy cows. We also conducted animal experiments in vivo by feeding rumen-bypassed niacin. Compared with those in the untreated mastitis group, the somatic cell counts (SCCs) and the expression of IL-6, IL-1β, and TNF-α in the blood and milk were lower. In vitro, we isolated the primary bovine mammary epithelial cells (BMECs) from the mammary glands of the healthy cows. The mRNA levels of , and autophagy-related genes were detected after adding niacin, shRNA, compound C, trans retinoic acid, 3-methyladenine to BMECs. Then GPR109A, AMPK, NRF-2, and autophagy-related proteins were detected by Western blot. We found that niacin can activate GPR109A and phosphorylate AMPK, and promote NRF-2 nuclear import and autophagy to alleviate LPS-induced inflammatory response in BMECs. In summary, we found that niacin can reduce the inflammatory response of BMECs through GPR109A/AMPK/NRF-2/autophagy. We also preliminarily explored the alleviative effect of niacin on mastitis in dairy cows.
乳腺炎是全球范围内每年导致重大经济损失的三种奶牛疾病之一。烟酸是一种重要的饲料添加剂，广泛用于奶牛营养。然而，烟酸作用于乳腺炎的机制尚不清楚。本研究旨在探讨烟酸缓解奶牛乳腺炎的乳腺上皮细胞炎症反应和抗乳腺炎的机制。收集未用烟酸（ = 3）和用烟酸（30 g/d， = 3）治疗以及健康奶牛（ = 3）乳腺炎奶牛的乳腺、奶和血液样本。乳腺炎奶牛乳腺中 GPR109A、IL-6、IL-1β 和 TNF-α 的表达明显高于健康奶牛乳腺。我们还通过给奶牛饲喂瘤胃旁路烟酸进行了体内动物实验。与未治疗乳腺炎组相比，血液和奶中的体细胞计数（SCC）和 IL-6、IL-1β 和 TNF-α 的表达降低。在体外，我们从健康奶牛的乳腺中分离出原代奶牛乳腺上皮细胞（BMECs）。在向 BMECs 中添加烟酸、shRNA、化合物 C、反式维甲酸和 3-甲基腺嘌呤后，检测 、自噬相关基因的 mRNA 水平。然后通过 Western blot 检测 GPR109A、AMPK、NRF-2 和自噬相关蛋白。我们发现烟酸可以激活 GPR109A 并磷酸化 AMPK，促进 NRF-2 核内易位和自噬，从而缓解 BMECs 中 LPS 诱导的炎症反应。总之，我们发现烟酸可以通过 GPR109A/AMPK/NRF-2/自噬减少 BMECs 的炎症反应。我们还初步探讨了烟酸对奶牛乳腺炎的缓解作用。
