AMPK-mTOR在牛磺酸调控有氧糖酵解缓解乳房链球菌感染中的作用机制研究

为探讨牛磺酸是否通过调控AMPK-mTOR（感知、调节物质和能量代谢的关键分子）来影响乳腺细胞中有氧糖酵解途径，进而全面调节宿主的物质及能量代谢，以缓解乳房链球菌感染引起的炎症。本研究拟将牛磺酸、乳房链球菌和重要乳腺细胞（Mφ、PMN及MECs）按一定的时序、组合共孵育，并适时激活/抑制糖酵解途径及AMPK、mTOR的表达与活性，通过比较各代谢途径关键酶上下游底物/产物浓度、酶活性、效应分子、胞内载菌量及细胞损伤等的变化，首先从细胞水平评价有氧糖酵解现象及AMPK、mTOR分子在牛磺酸缓解乳房链球菌感染过程中对乳腺细胞物质和能量代谢的影响及生物学意义，然后在动物上进行整体验证，最终达到全面阐明AMPK-mTOR在牛磺酸调控有氧糖酵解，缓解乳房链球菌感染中的作用机制的目的。研究的开展，将为乳房链球菌等胞内菌感染引起的乳腺炎的防控，提供新的思路及有效手段，对奶牛产业的健康发展具有重要的意义。

The goal of this study is to investigate whether AMPK-mTOR signaling, a pathway key to energy metabolism, could mediate the effects of taurine on the aerobic glycolysis pathway in mammary cells, allowing the host to alleviate Streptococcal breast infection through regulation of the substance and energy metabolism. In this study, important breast cells (Mφ, PMN and MECs) will be cultured with various combinations of taurine and Streptococcus uberis for various time periods. We will perturb the glycolysis pathway and the expression and activity of AMPK and mTOR. By monitoring the activities of enzymes functioning in the metabolic pathways, the levels of their substrates and products, effector molecules, intracellular bacterial load and the change of cell damage, our studies uncover the cellular and molecular mechanisms through which the glycolysis pathway and of AMPK/mTOR signaling mediate the effect of taurine in alleviating Streptococcal breast infection. Results from these in vitro experiments will be further validated by whole animal studies. Collectively, the above work will define the function of AMPK-mTOR as a mediator of taurine in attenuating mastitis caused by Streptococcus uberis, and identify novel strategy for prevention and control of intracellular bacteria such as Streptococcus uberis, which is of great significance for the development of the dairy industry.