类风湿关节炎（RA）属中医“痹证”范畴，脾虚是其基本病机之一。课题组前期研究发现，脾虚证小鼠肠道黏膜免疫失调可加重关节炎发病。新近研究表明，肠道菌群紊乱不仅是脾虚证的重要病理变化之一，而且参与RA发病。作为肠道微环境重要组成部分的肠道菌群和黏膜免疫均与RA发病密切相关。基于此，我们认为脾虚加重痹症与肠道微环境密切相关，并提出新的假说：脾虚状态下，肠道微环境的肠道菌群发生了紊乱，这种紊乱导致与之紧密联系的肠道黏膜免疫系统失调，进而加重了痹症。因此，本项目拟基于前期建立的DBA/1小鼠脾虚痹症（CIA）模型，运用宏基因测序结合生物信息学方法，绘制DBA/1小鼠脾虚痹症肠道菌群谱系，初步阐明其肠道微环境特征；采用流式细胞术、ELISA等方法，研究肠道菌群紊乱对肠道黏膜免疫系统的影响并进行性相关性分析。最后以芎附散为工具药，对脾虚加重痹症的机制进行反证。研究结果将为痹症从脾论治提供新的思路和靶标。

Rheumatoid arthritis (RA) is one of Bi syndrome in traditional Chinese medicine, and spleen deficiency is one of the basic pathogenesis of Bi syndrome. Our previous studies showed that the disorders of intestinal mucosal immune system under the condition of spleen deficiency can aggravate the progress of arthromyodynia. It was also reported that intestinal flora disturbance is not only an important pathological factor of spleen deficiency syndrome, but also involved in the pathogenesis of RA. As an important part of intestinal micro environment, intestinal flora and mucosal immunity are closely related to the pathogenesis of RA. Above all, we put forward the new hypothesis that the spleen deficiency could induce the aggravation of Bi syndrome (CIA): In the state of spleen deficiency, the disorder of intestinal flora leads to the disorder of intestinal mucosal immune system, which further aggravates the Bi syndrome. In the present research, the pre-established stable spleen deficiency CIA model of DBA / 1 mice and metagenomics sequencing technologies combined with bioinformatics method will be used to draw the intestinal bacteria group lineages and to elucidate intestinal micro environment characteristic of spleen deficiency with Bi syndrome. Flow cytometry and ELISA will be used to investigate the relationship and the effect of intestinal flora disturbance on intestinal mucosal immune system. Finally, Xiongfu powder will be used as the tool medicine to verify the mechanism of spleen deficiency aggravated Bi syndrome. The results will provide new ideas on the treatment of rheumatism from the spleen.