UPR 在奶牛子宫内膜炎症反应调控中的作用及其机制

Inflammation-induced endometrial injury and dysfunction is the main reason of causing infertility in animals. Unraveling the regulatory mechanism of endometrial cell inflammations is of great significance to improve the pregnancy rate and ensure the health of the fetus. In recent years, the role of the unfolded protein response (UPR) in the inflammatory regulation has become a research hot spot. Using the immunohistochemistry, DGGE, qRT-PCR, Western Blot, and ELISA techniques, we will first detect and analyze the correlation between postpartum uterine infection and UPR in dairy cows, then we construct the cell lines interfering or overexpressing the key genes of UPR, and the endometrial stereoscopic/3D culture models, taking dairy cow endometrial epithelial cell line and endometrial stromal cell line as the research subjects. In addition, we will detect the changes of key factors in UPR signaling pathway and inflammatory factors of endometrial cell during infection processes of the main pathogens and their virulence factors. In this study, the effect of UPR on the regulation of endometritis will be parsed, and the pathogenesis of UPR coupling inflammation reaction participating in endometrial cells infection will be unraveled. Therefore, this study will provide us theoretical and experimental basis for a comprehensive understanding on regulatory networks of endometritis, and exploring new targets of prevention and control of dairy cow uterine inflammation related reproductive disturbance.

炎症引起的子宫内膜细胞损伤和机能紊乱是造成动物不孕的主要原因，深入揭示子宫内膜细胞炎症的调控机制，对于提高妊娠率、保证胎儿的健康具有重要的意义。未折叠蛋白反应（UPR）在炎症调控中的作用是近年研究的热点。本项目拟通过免疫组化、DGGE、qRT-PCR、Western blot、ELISA等技术，在测定分析奶牛产后子宫感染与UPR相关性的基础上，以永生化奶牛子宫内膜上皮和基质细胞系为研究对象，构建UPR关键基因干扰/过表达细胞株和子宫内膜3D培养模型，检测主要病原菌及其毒力因子侵染过程中子宫内膜细胞UPR通路关键基因和炎性因子的变化；解析UPR在子宫内膜炎症调控中作用，揭示UPR偶联炎症反应参与子宫内膜细胞感染的发病机制。为全面认识子宫内膜炎症的调控机理、探寻奶牛子宫炎症性繁殖障碍的防控新靶点提供理论和试验依据。

本项目通过免疫组化、DGGE、qRT-PCR、Western blot、ELISA等技术，在测定分析奶牛产后子宫感染与UPR相关性的基础上，以永生化奶牛子宫内膜上皮和基质细胞系为研究对象，构建UPR关键基因干扰/过表达细胞株培养模型，检测主要病原菌及其毒力因子侵染过程中子宫内膜细胞UPR通路关键基因和炎性因子的变化；解析UPR在子宫内膜炎症调控中作用，揭示UPR偶联炎症反应参与子宫内膜细胞感染的发病机制。为全面认识子宫内膜炎症的调控机理、探寻奶牛子宫炎症性繁殖障碍的防控新靶点提供理论和试验依据。发表研究论文17篇，培养博士研究生5名，硕士研究生6名。