高产奶牛因饲喂高比例精料日粮，临床上常发生亚急性瘤胃酸中毒(SARA)。SARA状态下瘤胃中产生的脂多糖（LPS）被吸收后由门静脉进入肝脏引起炎症反应。前期研究发现，转录因子FOXA2可以减轻肝脏炎性因子的分泌，但其确切机制尚不清楚。本项目以奶山羊为模型动物，人工诱发SARA，手术安装门静脉和肝静脉血管瘘，应用肝脏组织活体取样技术、信号通路分析、免疫荧光观察、染色质重塑分析、DNA甲基化分析、染色质免疫共沉淀等方法研究： LPS对肝脏组织中FOXA2基因表达的转录调控；FOXA2对肝脏组织中TLR4-NF-κB信号通路的影响；通过门静脉LPS灌注试验进一步研究FOXA2对肝脏炎症反应的调节机制；体外研究FOXA2对肝细胞炎症反应的分子机制；通过上调FOXA2表达，干预SARA引起的肝脏炎症反应。研究结果可为兽医临床上SARA引起的奶牛肝脏炎症的防治和肝脏功能的修复提供新的靶点和理论依据。

High-yielding dairy cows are often fed with high ratio concentrate diet, and usually suffer from subacute ruminal acidosis (SARA) in veterinary clinic. Under SARA status, lipopolysaccharide (LPS) produced in the rumen is absorbed and enter the liver from portal vein, thus cause liver inflammatory response. Our initial study showed that transcription factor FOXA2 could reduce inflammatory cytokine secretion in the liver of dairy cows. However, the exact mechanism involved in it is still unclear. In this project, dairy goats will be used as model. SARA will be induced by feeding high ratio concentrate diet. Portal and hepatic catheters will be inserted by surgical operation. Punch biopsy of liver tissue, signal pathway analysis, immunofluorescent observation, chromatin compaction assay, DNA methylation assay, chromatin immunoprecipitation assay techniques will be used in this project. The study of the project includes: transcription control of LPS on gene expression of FOXA2 in liver tissues; effects of FOXA2 on TLR4-NF-κB signal pathway of liver tissues; regulation mechanism of FOXA2 on inflammatory response in liver will be further revealed by LPS infusion experiment from portal vein; molecular mechanism of FOXA2 on inflammatory response of primary hepatocytes in vitro; by up-regulating FOXA2 expression to interfere inflammatory response of liver caused by SARA. The results of this project will provide new target point and theoretical basis for veterinary clinical control of liver inflammation caused by SARA and restoration of liver function in dairy cows.