STAT1-ROS环路上调OxPLs介导的氧化应激加重LPS诱导奶牛乳腺上皮细胞炎性损伤的分子机制

如何安全有效的防治奶牛乳腺炎是全世界亟待解决的科学问题。最新研究显示，活性氧 （ROS）导致的氧化磷脂（OxPLs）浸润即氧化应激反应在多种炎症性疾病中发挥关键作用，然而其在奶牛乳腺炎进程中的调节机制尚不明确。前期研究显示，阻断STAT1通路在降低奶牛乳腺炎模型内炎性因子表达的同时降低了ROS/OxPLs的生成。基于此并结合国内外进展，我们提出假设，STAT1-ROS环路上调氧化应激加重LPS诱导奶牛乳腺上皮细胞（BMECs）炎性损伤的分子机制。首先，通过EMSA和RNAi等技术，在体外BMECs炎症模型上证实存在STAT1-ROS环路调控氧化应激反应；其次，采用IF和RT-PCR等技术探索氧化应激形成的OxPLs加重BMECs炎性损伤的分子机制；最后，在小鼠乳腺炎模型上一一验证。从而揭示STAT1-ROS环路调控氧化应激在奶牛乳腺炎发生发展中的作用及其分子机制，为乳腺炎的防治提供新靶标。

The emergence of drug-resistance strain and antibiotic residue in milk highlight the need for more safe and effective therapy of mastitis in the whole world. According to the recent study, reactive oxygen species (ROS) mediate oxidized phospholipids (OxPLs) infiltration which also called as oxidative stress is a key element in the progress of inflammatory diseases. Whether this mechanism participates in mastitis is still unknown. Previous studies have shown that after blocking the activation of the STAT1 pathway, oxidative stress and inflammatory response in bovine epithelial cells (BMECs) are significantly reduced. Based on domestic and foreign research progress, we propose the hypothesis that STAT1-ROS cycle extends LPS induced bovine mammary epithelial cells inflammatory injury through oxidative stress. First, EMSA and RNA silencing techniques were used to confirm the existence of STAT1-ROS cycle in BMECs inflammation model; Second, immunofluorescence and qRT-PCR were used to explore the molecular mechanism of OxPLs in the developing of BMECs inflammatory response; finally, validation in mouse mastitis models revealed the regulatory role of STAT1-ROS cycle in the occurrence and development of inflammation, and provided new targets for the mastitis therapy.