外排性药物转运体BCRP的表达变化会引起其底物药物生物利用度改变或药物间相互作用发生，因此阐明其表达调控机制是兽医临床合理用药及新药研发的重要切入点。申请者前期研究发现鸡BCRP基因启动子区域存在核受体CXR结合位点，且该位点的突变显著降低鸡BCRP基因启动子活性，推测CXR正向调控鸡BCRP表达。本项目拟通过凝胶迁移、染色质免疫共沉淀、定点突变、siRNA干扰和报告基因等方法研究CXR对鸡BCRP基因表达调控作用，并通过构建细胞模型筛选CXR抑制剂，进一步探讨CXR抑制剂对鸡BCRP底物药物吸收及生物利用度的影响。该项目研究结果可完善鸡BCRP表达调控机制理论，并为基于BCRP途径开发适合鸡临床群体给药的高生物利用度口服制剂及指导临床合理用药提供新思路，故具有重要的理论和实践意义。

The expression change of chicken breast cancer resistance protein (BCRP) may affect the drug pharmacokinetics and mediate drug–drug interactions, therefore, it is the key to clarify the regulatory mechanism of BCRP gene expression for rational drug use and new drug research. The applicant's previous study found that there was a CXR binding site in chicken BCRP gene promoter and the mutation of this site caused a significant decrease of BCRP gene promoter activity. It is speculated that CXR is positively regulating the expression of chicken BCRP. This project aims to study the regulation of chicken BCRP gene expression by CXR through electrophoretic mobility shift assay, chromatin immunoprecipitation, site directed mutagenesis, siRNA interference and luciferase reporter assay. Further to study the effect of selected CXR inhibitor on the absorption and bioavailability of chicken BCRP substrate drug through the constructed cell model. The research reveals the regulation mechanism of chicken BCRP expression, in addition, provide new ideas for rational drug use and improving the bioavailability of substrate drugs based on BCRP pathway.