寒地奶牛重要代谢病先天免疫稳态失衡调控机理研究

寒地规模化场围产期奶牛存在显著的代谢病（酮病、低钙血症、亚急性瘤胃酸中毒等）与炎症性疾病（乳房炎、子宫内膜炎、蹄叶炎等）高发并发群发临床关联特征。为此，项目拟聚焦围产期奶牛代谢病先天免疫稳态调控失衡，围绕营养代谢-先天免疫-炎性反应这一主线，通过体内和体外实验，从外周血和靶组织乳腺两个层面，利用单细胞测序、组学等交叉融合技术，分析酮病、低钙血症和亚急性瘤胃酸中毒的主要病理学因素（高NEFA、高BHBA、低Ca2+和高LPS）对中性粒细胞、M1和M2巨噬细胞等先天免疫重要效应细胞稳态的影响；明确SREBP-1c-ROS-NFκB/NLRP3、SOCE、AKT/mTOR等通路在介导代谢病引发先天免疫抑制的机理；阐明代谢病奶牛乳腺组织中性粒细胞NETs活化巨噬细胞“递送”机制；全景式揭示代谢病中性粒细胞和巨噬细胞免疫稳态失衡调控网络，为从营养和免疫双重角度防治奶牛代谢病与炎症疾病奠定理论基础。

The metabolic diseases (ketosis, hypocalcemia, subacute ruminal acidosis, etc) and inflammatory diseases (mastitis, endometritis, and laminitis) during the transition period of dairy cows in cold region large-scale farm has a high and co-occurrence onset characteristics. The project focus on transition period dairy cows with metabolic diseases induced the innate immunity imbalance. Around the main line of nutrition and metabolism, innate immunity, and inflammation, through in vivo and in vitro experiments, from two aspects of peripheral blood and target tissue mammary gland, by using single cell sequencing, transcriptomics, proteomics and other technologies, the project addresses the effect of high NEFA, high BHBA, low Ca2+ and high LPS on neutrophil, M1 macrophages, M2 macrophages in dairy cows with ketosis, hypocalcemia, subacute ruminal acidosis, The project will be evaluated the regulatory mechanism of SREBP-1c-ROS-NFκB/NLRP3, SOCE, AKT/mTOR on innate immunosuppression in dairy cows with ketosis, hypocalcemia, subacute ruminal acidosis, reveal the immunosuppressed “delivery” mechanism of neutrophil activated macrophages, construct the panoramic immune regulatory network of neutrophils and macrophages in dairy cows with ketosis, hypocalcemia, subacute ruminal acidosis. Furthermore, it will provide the nutritional and immune theoretical foundation for prevention and control of nutritional and metabolic diseases and inflammatory diseases.