黄芪赤风汤提取物对早期RA特异性生物标记物的影响及其药效物质基础研究

Rheumatoid arthritis (RA) is a common clinical disease, and up to now there is no ideal therapeutic drug. We have found that the extract of Huangqichifeng decoction has a clear anti RA effect in previous study. Huangqichifeng decoction is one of the commonly used prescriptions in clinic. However, its mechanism of anti RA action is not very clear. This research subject will reveal the efficacy of Huangqichifeng decoction through the intervention effect on the specific biomarker and the pharmacodynamic material basis in early stage RA. We will take CP, the specific biomarker of early stage RA, as the breakthrough point, through the establishment of arthritis rat model induced by CFA, and developing stable isotopic dilution analysis liquid chromatography tandem mass spectrometry to determine the CP content in vivo, the influence of drugs in early stage RA will be evaluated. In addition, the material basis for the efficacy of drugs will be illustrated through the dynamic chemical characterization of the metabolites and the pharmacokinetic of the active components in the rat model of arthritis by LC-MS-IT-TOF. Finally, we will clarify the mechanism of efficacy of Huangqichifeng decoction in early stage RA, and provide experimental evidence for the clinical treatment for RA.

类风湿性关节炎（RA）是临床常见疾患，目前尚无理想治疗药物，我们前期研究发现黄芪赤风汤提取物具有明确的抗RA作用。本方是临床常用方剂之一，但其抗RA的作用机制并不十分清楚。本课题从黄芪赤风汤对早期RA特异性生物标记物的干预作用和药效物质基础两方面揭示其治疗早期RA功效。以早期RA特异性生物标记物CP为切入点，通过建立CFA诱导的关节炎大鼠模型，以稳定同位素稀释液相色谱质谱联用法测定体内CP含量，评价药物对早期RA的治疗作用，并以LC-MS-IT-TOF技术对复方提取物在关节炎大鼠模型的代谢物进行动态化学表征，研究活性成分药代动力学特征，进而阐明药物的药效物质基础。最终阐明黄芪赤风汤治疗早期RA的作用机制，并为其用于RA临床治疗提供实验依据。

类风湿性关节炎（RA）是临床常见疾患，目前尚无理想治疗药物，前期研究发现黄芪赤风汤提取物具有明确的抗RA作用。本方是临床常用方剂之一，但其抗RA的作用机制并不十分清楚。本项目从黄芪赤风汤对早期RA特异性生物标记物的干预作用和药效物质基础两方面揭示其治疗早期RA功效。以早期RA特异性生物标记物CP为切入点，通过建立胶原诱导性关节炎大鼠模型，评价药物对早期RA的治疗作用。结果表明黄芪赤风汤降低关节滑液中瓜氨酸化组蛋白H3含量，能够下调血清中相关细胞因子的表达，减轻关节的病理改变，提示有较好的抗炎作用。以高分辨质谱技术对复方提取物在大鼠血浆、尿液和粪便中的代谢物进行动态化学表征，利用代谢组学数据分析软件，初步研究发现给药后，血浆、尿液、粪便中原型成分及代谢物分别14个、34个和52个。利用LC-MS技术研究复方中多成分药代动力学特征。本项目研究结果有利于客观阐述黄芪赤风汤治疗早期RA的作用机制及药效物质基础，并为其用于RA临床治疗提供实验依据。