基于Ephrin B2调控的TGF-β1/Smad3信号通路探讨化瘀通络方改善宫腔粘连纤维化的机制

宫腔粘连（IUA）是子宫内膜修复障碍结局，是一种纤维化疾病。Ephrin B2被认为是肌成纤维细胞活化的新靶点，参与多器官组织纤维化，但在IUA纤维化中的作用尚不清楚。前期实验研究证明，化瘀通络方（丹枝饮）可以改善盆腔微循环血流，调控MAPK经典炎症通路而起到抗纤维化作用；同时，在人IUA样本和IUA大鼠子宫组织中发现Ephrin B2和TGF-β1、p-Smad3呈高表达。在此基础上，提出化瘀通络方可通过调控Ephrin B2介导TGF-β1/Smad3信号通路而改善IUA纤维化的假说。围绕假说，本研究通过动物和细胞实验观察Ephrin B2、TGF-β1/Smad3信号通路和纤维化因子的表达。同时，采用慢病毒感染技术，验证Ephrin B2和IUA纤维化的关系，并进一步阐明化瘀通络方调控IUA纤维化的具体机制。本项目研究结果有望为中医药防治宫腔粘连的临床应用提供新的实验依据。

Uterine adhesion (IUA) is the outcome of endometrial repair disorders and belongs to a kind of fibrotic disease. Ephrin B2 is considered as a new target for myofibroblast activation and participates in multiple organ fibrosis, but its role in IUA fibrosis is not clear. Our previous experimental studies have demonstrated that dissolving stasis and dredging collateral recipe (Danzhi yin) could improve the pelvic microcirculation and play an anti-fibrosis effect through MAPK pathway. Moreover, high level of Ephrin B2 and TGF- β1、Smad3 expression was found in human IUA samples. On this basis, this study proposes the hypothesis that Danzhi yin recipe can improve IUA fibrosis by regulating Ephrin B2-mediated TGF- β1/Smad3 signal pathway. According to the hypothesis, this study will test the expression of Ephrin B2, TGF-β1, Smad3 and fibrosis factors through animal and cell experiments. Meanwhile, lentivirus transfection technique will be used to verify the relationship between Ephrin B2 and IUA fibrosis, and further elucidate the specific mechanism of Danzhi yin recipe in regulating IUA fibrosis. The results of this research are expected to provide a new experimental basis for the clinical application of traditional Chinese medicine in the prevention and treatment of uterine adhesion.