基于TGF-β/Smad信号通路研究补中益气汤调节Treg与Th17细胞平衡治疗桥本氏甲状腺炎的作用机制

桥本氏甲状腺炎(HT)属于器官特异性自身免疫性疾病，目前尚无免疫治疗药物。Treg与Th17细胞平衡失调在发病中起关键作用。我们前期研究发现：补中益气汤能降低甲状腺抗体、调节Treg与Th17细胞平衡，上调TGF-β、Foxp3 mRNA水平，对本病有治疗作用，但其具体机制不明。TGF-β/Smad信号通路是调控Treg与Th17细胞平衡的关键途径。由此我们提出假说：补中益气汤治疗HT的机制可能是基于TGF-β/Smad信号通路调控Foxp3，进而调节Treg与Th17细胞平衡。本课题以EAT大鼠为实验模型结合细胞实验，通过基因组学、蛋白组学等方法检测TGF-β/Smad通路关键转录因子和蛋白的表达、Treg与Th17细胞分布情况等，研究补中益气汤基于TGF-β/Smad信号通路调控下治疗HT的作用机制和靶点。该研究对科学阐明中医药干预HT的作用机制具有重要意义。

Hashimoto's thyroiditis (HT) is a common and frequently-occurring clinical disease, which belongs to organ-specific autoimmune disease. Currently, there are no immunomodulatory drugs for this disease.Imbalance between Treg and Th17 cells plays a key role in the pathogenesis of HT.Our previous study found that buzhong yiqi decoction(BZYQD) can lower TPOAb and TGAb, alleviate lymphocyte infiltration, regulate the balance between Treg and Th17 cells, and up-regulate the levels of TGF-β and Foxp3 mRNA.Although BZYQD has therapeutic effects on hashimoto's thyroiditis, the specific mechanism is still unclear.The TGF-β/Smad signaling pathway regulates Foxp3, which is a key transcription factor for the balance between Treg and Th17 cells.Therefore, we hypothesized that the mechanism of BZYQD in the treatment of HT may be the regulation of Foxp3 based on the TGF-β/Smad signaling pathway, which further regulates the balance between Treg and Th17 cells and improves the immune function.In this study, EAT rats experiment combined with cell experiment, testing transcription factors and proteins in the TGF-β/Smad pathway, as well as the distribution of Treg and Th17 cells by genomics, proteomics and other methods, so as to study the mechanism and target of buzhong yiqi decoction in the treatment of hashimoto's thyroiditis based on the regulation of TGF-β/Smad signaling pathway.This study is of great significance in expounding the mechanism of TCM intervention in HT and providing scientific basis for the treatment of hashimoto's thyroiditis with TCM.