基于“脾滋胎气”补脾益气法靶向PD-1/PD-L1通路调节蜕膜巨噬细胞极化干预TAI合并流产机制研究

甲状腺自身免疫（TAI）与妊娠不良结局相关性是本领域研究热点，其中单纯甲状腺抗体增高（单纯TAI）可不依赖TSH降低而独立导致流产发生，目前尚无充分证据表明LT4对妊娠维持有效。蜕膜巨噬细胞极化失衡为本病西医病理基础，脾气不足、胎失滋养为中医病机，两者存在一定相关性。故申请人以“脾滋胎气”理论为基础，取“滋化源、举中气、御邪气”之意，采用中医经典方剂“补中益气汤”干预本病，前期研究表明，本方剂在TAI防治中具有良好疗效。为进一步探索疗效机制，申请人提出科研假说：补中益气汤能够通过激活PD-1/PD-L1信号通路，经激活胞内PI3K/Akt/mTOR、MEK/ERK信号通路转导，抑制蜕膜巨噬细胞糖酵解代谢，维持蜕膜巨噬细胞极化平衡，防治TAI合并流产。申请人拟从体内、体外多水平开展实验，重点挖掘TAI合并流产过程中蜕膜巨噬细胞代谢、极化特点及其通路调控机制，从而为中药新药研制奠定基础。

The relationship between thyroid autoimmunity (TAI) and adverse pregnancy outcomes is a research hotspot of the endocinology. The increase of thyroid antibody alone can lead to abortion without the decrease of TSH independently. There is no sufficient evidence to show that LT4 is effective in maintaining pregnancy under this stituation .The imbalance of decidual macrophage polarization is the pathological basis of Western medicine, meanwhile, the deficiency of spleen qi and fetal loss of nourishment are the pathogenesis pattern of the traditional Chinese medicine, and there is definitely a certain correlation between the two theory. Therefore, based on the theory of "spleen nourishing fetal Qi", the applicant adopted the classical TCM prescription "Buzhong Yiqi Decoction" to intervene the disease, taking the method of "nourishing the source, lifting the middle Qi and resisting the evil Qi". The previous research showed that this prescription had good curative effect in the prevention and treatment of TAI. In order to further explore the mechanism of curative effect, the applicant proposed a scientific research hypothesis: "Buzhong Yiqi Decoction" can inhibit glycolysis metabolism of decidual macrophages, maintain polarization balance of decidual macrophages, and prevent abortion of TAI by activating PD-1 / PD-L1 signal pathway and PI3K / Akt / mTOR and MEK / ERK signal pathway. The applicant intends to carry out experiments at multiple levels in vivo and in vitro, focusing on the metabolism, polarization characteristics and pathway regulation mechanism of decidual macrophages in the process of TAI complicated with abortion, so as to lay a foundation for creating the new traditional Chinese medicine.