基于CXCL12/CXCR4轴的雷公藤多苷预防类风湿关节炎并发动脉粥样硬化的生物学机制研究

Cardiovascular disease (CVD) is the leading cause of death in rheumatoid arthritis (RA) patients, and the atherosclerosis (AS) is the main reason of CVD and therefore is of great clinical significance on prevention of the AS complication of RA in the early stage of the disease. In our previous studies, it was found that tripterginum wilfordii polyglycoside (TWP) demonstrates obvious inhibitory effect on the mRNA expressions level of CXCL12 and CXCR4 in blood cells in collagen-induced arthritis (CIA) rats. The CXCR4 axis plays an important role in the early stage of atherosclerosis. Based on the above evidence, we propose that TWP could prevent the AS complication in RA patients. The study uses the male C57Bl/6J mice as an experiment animal with CIA add high cholesterol diet (HD) model, and then observes the effect of the formation of aortic atherosclerotic plaque treated with TWP. Through testing the key genes and protein expression, protein activity status and location of CXCR4 axis downstream pathways in the serum and aorta samples, the research explores the biological mechanisms of preventing the early-onset of AS in RA patients with TWP, and can provide reference for the clinical application of TWP in the prevention of the early-onset of atherosclerosis in RA patients.

心血管疾病是类风湿关节炎（RA）患者死亡的主要原因，而动脉粥样硬化（AS）又是心血管病的主要原因，故在RA发病早期有效预防AS的发生具有重要临床意义。课题组在前期雷公藤多苷（TWP）治疗胶原诱导的关节炎（CIA）动物实验中，发现TWP对动物血细胞CXCL12和CXCR4的mRNA有明显抑制作用，而CXCR4轴调控的信号通路在AS发生、发展进程中起了重要的推动作用。为此，本研究提出TWP可能通过抑制CXCL12/CXCR4轴达到预防RA并发AS的作用。研究以雄性C57Bl/6J小鼠CIA+高脂饮食（HD）为动物模型，观察雷公藤多苷对模型动物主动脉粥样硬化斑块形成的影响，通过检测血清、主动脉等样本CXCR4轴下游通路的关键基因、蛋白表达，蛋白活性状态以及表达部位等，探究雷公藤多苷预防RA并发AS的生物学机制。研究可为临床应用TWP预防RA并发AS的发生提供借鉴。