奶牛乳腺炎世界范围内高发，其防治是国际研究的热点。已证实在炎症反应中，HSP72和IRAK-M表达均升高并抑制炎症，而HSP72又间接影响IRAK-M的表达，但HSP72和IRAK-M抑制炎症信号转导机制尚不清楚。本研究拟以HSP72与IRAK-M存在调控关系，且负反馈调控TLR4信号转导为理论假说。从HSP72和IRAK-M抑制TLR4炎症信号转导为切入点，采用分子生物学和细胞生物学等研究手段，观测奶牛乳腺炎症组织（体内）和乳腺上皮细胞炎症模型（体外）中HSP72和IRAK-M相互调控关系，检测乳腺上皮细胞炎症模型中TLR4信号通路中关键因子（IRAK-4/1、TRAF6、NF-κB、p38和JNK）和炎症因子（IL-1β、IL-6、IL-8和TNFα）的变化。分析HSP72/IRAK-M抑制奶牛乳腺上皮细胞炎症TLR4信号转导机制，为寻找治疗奶牛乳腺炎药物靶点提供理论与实验依据。

Mastitis in dairy cow is in a high incidence all over the world and its prevention and treatment have been becoming an increasingly hotspot of international research. It has been already proved that both HSP72 and IRAK-M increases their expressions in the inflammation, which in turn inhibit inflammatory process. HSP72 influences IRAK-M expression indirectly. However, the signal transmission mechanism of HSP72 and IRAK-M inhibiting inflammatory process is not clear. We hypothesize that HSP72 and IRAK-M mutual regulate and control each other, which negative feedback regulate TLR4 signal transmission mechanism. The research aims to explore the mechanism of HSP72 and IRAK-M in the inhibition of TLR4 inflammation signal transmission. We will study the mutual regulating relationship between HSP72 and IRAK-M both in the inflammation tissue of cow mammary gland (in vivo) and in the inflammation model of epithelial cells（in vitro）using advanced technologies in modern molecular biology and cytobiology, as well as the dynamic changes of the key molecules (IRAK-4/1, TRAF6, NF-κB, p38 and JNK) expression in the TLR4 signal pathway and inflammatory factor (IL-1β, IL-6, IL-8 and TNFα) in the inflammation model of epithelial cell. The correlations between these measured indicators and HSP72/IRAK-M inhibiting TLR4 signal transmission mechanism in both mammary gland and in the inflammation model of epithelial cells will be analyzed. The results will provide a theoretic and experimental base for finding drug target in treating clinical mastitis of dairy cow.