黄芩苷白术多糖配伍上调Treg细胞治疗免疫性RSA的分子机制研究

Immune-mediated recurrent spontaneous abortion（RSA） manifested as a lack of immune tolerance is clinical refractory disease and its incidence was increased year by year. As “the God Tocolytic Medicine”, combination of Baikal skullcap and Atratylodes, known as "Baizhusan", was used to treat abortion for a long time, which was recorded in the Fu Ren Da Quan Liang Fang in the Song Dynasty. The composition of Traditional Chinese Compound Prescription is very complication and it is difficult to explore its concrete mechanism. The monomer has exact chemical structure and it is convenient to investigate the precise mechanism of its action. Previous studies found that baicalin and atractylodes macrocephala polysaccharide was the main Immune regulation related ingredient of Baikal Skullcap and Atractylodes respectively, which could all promote immune tolerance. Treg cells play a key role in the immune tolerance of pregnancy. Preliminary experiment showed that combination of baicalin and Atractylodes macrocephala polysaccharide possessed effectiveness for treatment of immune-mediated RSA mice. In additional, the combination of baicalin and Atractylodes macrocephala polysaccharide could also promote Treg proliferation in immune-mediated RSA mice. Activation of Treg cells was mainly mediated by STAT5 signaling pathway with IL-2 and TGF-β costimulation. This current project intends to prove that combination of baicalin and Atractylodes macrocephala polysaccharide could increase TGF-β, IL-2 levels, and then activate Treg cells through STAT5 signaling pathway in the mouse spleen naïve CD4(+) T cells and CBA/J*DBA/2 immune-mediated RSA mice. We focus on the effectiveness in the treatment of immune-mediated RSA by combination of baicalin and Atractylodes macrocephala polysaccharide through enhancing immune tolerance. This research will provide theoretical basis and precise mechanism for treatment of immune-mediated RSA by the combination of Baicalin and Atractylodes macrocephala polysaccharide.

免疫性复发性流产（RSA）是难治性疾病，发病率逐年升高，表现为缺乏免疫耐受。黄芩白术为“安胎圣药”，宋代《妇人大全良方》即有仅含黄芩白术配伍的白术散，主治胎动不安。但中药复方成分复杂，而单体化学结构确切，有助于精确的机制研究。研究发现黄芩苷和白术多糖分别是黄芩和白术发挥免疫调节的物质基础，可促进免疫耐受。Treg细胞在妊娠免疫耐受中发挥关键作用，预实验显示黄芩苷白术多糖配伍治疗免疫性RSA小鼠有效，且可促进其外周血Treg细胞增殖。Treg细胞的活化主要通过IL-2和TGF-β介导的STAT5信号通路。本课题拟用小鼠脾脏naïve CD4(+) T细胞和CBA/J*DBA/2免疫性RSA孕鼠模型验证黄芩苷白术多糖配伍通过增加IL-2、TGF-β的分泌，增强STAT5信号通路活性，促进Treg细胞活化，促进免疫耐受，治疗免疫性RSA。本课题将为黄芩苷白术多糖配伍治疗免疫性RSA提供理论依据。

免疫性复发性流产（RSA）是难治性疾病，发病率逐年升高，表现为缺乏免疫耐受。黄芩白术自古被称为“安胎圣药”，仅含黄芩白术配伍的白术散可以主治胎动不安。但中药复方成分复杂，而单体化学结构确切，有助于精确的机制研究。本课题首次以黄芩苷和白术多糖为切入点，探寻黄芩和白术发挥免疫调节的物质基础。用小鼠脾脏naïve CD4(+) T细胞和免疫性RSA孕鼠模型（CBA/J*DBA/2）验证黄芩苷白术多糖配伍通过增加IL-2、TGF-β的分泌，增强STAT5信号通路活性，促进Treg细胞活化，促进免疫耐受，治疗免疫性RSA。为黄芩苷白术多糖配伍治疗免疫性RSA提供理论依据，为深入研究免疫性RSA中药复方的药效及机制提供参考经验，为药对配伍研究提供示范性研究，进一步验证祖国医学经典理论的学术价值。