Regulation of systemic and reproductive tract inflammation in dairy cows

这项研究计划将使加拿大13,000个奶牛场的近100万头泌乳奶牛受益，以及全球奶牛业中更多的奶牛，每年约有三分之一的奶牛因某种形式的生殖道疾病而生育力下降。虽然这些情况通常不会直接降低动物福利，但对生产者来说，它们在经济上代价高昂，而且不能怀孕最终将导致奶牛被赶出畜群。***炎症是产犊后子宫愈合的必要部分，但如果炎症过度或持续，可能是有害的，而不是有益的。由此看来，生殖道外代谢引起的全身性炎症（即脂肪动员和肝功能）可能至少与生殖道内细菌和炎症反应的局部相互作用同等重要。然而，代谢性炎症的作用仍有待量化，这是本研究计划的目标。要做到这一点，需要更好地了解采食量、能量供应和炎症之间的关系。***本研究计划的目标是：***1。描述奶牛妊娠最后几周采食量普遍减少与全身炎症指标增加之间的关系***2。目的：探讨策略抗炎治疗减少代谢道和生殖道炎症的能力和效用。为了研究改善哺乳早期能量供应对改善炎症状态的能力***在该研究计划的五年时间里，我们将进行三个密集的研究，这些研究相互促进，以实现目标。我们将使用经过验证的能量代谢、炎症、免疫功能和生殖道健康的微创标志物，试图解开采食量减少和全身炎症增加的关系，并测试抗炎治疗是否能缓解这些不良症状。接下来，我们将建立一个概念，证明全身抗炎治疗可以帮助减少生殖道炎症。最后，我们将研究减少炎症和增加能量供应对全身和局部生殖炎症和健康的单独和联合影响。该项目将培养2名研究生和6名本科生，掌握各种科学技术，使他们能够在加拿大经济中日益增长和日益复杂的动物农业部门从事以科学为基础的职业

This research program will benefit the nearly 1 million lactating dairy cows on 13,000 dairy farms in Canada, and many more in the global dairy industry, approximately one-third of which have their fertility reduced by some form of reproductive tract disease each year. While these conditions are generally not considered to reduce animal welfare directly, they are economically costly to producers, and failure to become pregnant will ultimately cause a cow to be removed from the herd.***Inflammation is a necessary part of uterine healing after calving, but*if inflammation is excessive or persistent it may be harmful rather than*helpful. It appears that systemic inflammation due to metabolism*outside the reproductive tract (i.e. fat mobilization and liver*function) may be at least as important as the local interactions of*bacteria and inflammatory response in the reproductive tract. However,*the contribution of metabolic inflammation remains to be quantified and*this is a target of the present research program. To do so will require a better understanding of the relationships between feed intake, energy supply, and inflammation.***The objectives of this research program are: ***1. To describe the relationship between the common decrease in feed intake and increased indicators of systemic inflammation in the last weeks of pregnancy in dairy cows***2. To establish the ability and utility of strategic anti-inflammatory therapy to reduce metabolic and reproductive tract inflammation ***3. To investigate the ability of improved energy supply in early lactation to improve inflammatory status***Over the five years of this research program, we will conduct three intensive studies which build on each other to achieve the objectives.  We will use validated, minimally-invasive markers of energy metabolism, inflammation, immune function, and reproductive tract tract health to try to disentangle decreases in feed intake and increases in whole-body inflammation and to test whether anti-inflammatory therapy can relieve undesirable symptoms of these.  Next we will establish proof of concept that systemic anti-inflammatory treatment can helpfully reduce inflammation in the reproductive tract.  Finally we will investigate the separate and joint effects of reducing inflammation and providing increased energy supply on whole-body and local reproductive inflammation and health.  This program will train 2 graduate and 6 undergraduate students in a wide variety of scientific techniques that will position them well for science-based careers in the growing and increasingly sophisticated animal agriculture sector of the Canadian economy.**