蹄叶炎是严重危害我国奶牛健康的一类疾病。我们及他人研究发现，亚急性瘤胃酸中毒（SARA）致奶牛蹄组织中基质金属蛋白酶MMP-2与MMP-9的酶活性升高，蹄组织结构受损，奶牛发生蹄叶炎，但其中的确切机制与干预措施尚不清楚。本课题拟在此基础上，通过SARA诱导蹄叶炎试验及体外建立蹄角细胞受损模型，应用Real-time PCR、Western blot和免疫组化等方法：1、解析SARA引发的炎症反应对蹄组织中JAK/STAT3信号通路活化的影响；2、从转录、酶原活化和酶活抑制三个层面，阐明蹄组织中JAK/STAT3通路对MMP-2/9酶活性的调控作用与机制；3、查明槲皮素干预SARA下蹄组织中MMP-2/9酶活性升高的效应及其信号转导机制。课题将在组织、细胞和分子水平上阐明SARA诱发蹄叶炎的机制，并为蹄叶炎的防治提供思路和理论依据。

Laminitis is one of the most important disease issues of high producing dairy cows in China. Previous studies showed that subacute rumen acidosis(SARA) can improve the matrix metalloproteinase 2 (MMP-2) and matix metallopoteinase 9 (MMP-9) activity in lamina tissue, this lead to the lamina dysfunction of the barrier function and connection, and laminitis may occur. However, there is little research on the exploration of the exact mechanism of the increase in MMP activity caused by SARA, and the future preventative measures are not yet clear. Based on these previous researches, three research objectives have been identified for this research project, with the hope that the outcome will reveal the mechanism of the laminitis occurrence induced by the SARA at the cellular and molecular level, and bring the dairy industry closer to finding an effective prevention strategy. The first goal of this project is to examine the effect of inflammation induced by SARA on the activation of JAK/STAT3 signalling pathwary. The second goal was to determine the role of JAK/STAT3 signalling pathway in the regulation of the activity of MMP-2 and MMP-9 in lamina tissue at the levels of transcriptional regulation, zymogen activation and enzyme inhibition in a laminitis model. The third goal is to test the effects of quercetin as a feed additive in preventing the increase in the activity of MMP-2 and MMP-9 in lamina tissue, and to explore the signalling pathway involved in the reduction of MMP-2 and MMP-9 activity induced by quercetin addition during SARA.