基于VEGF165a/VEGF165b-VEGFR1-STAT3信号通路研究清肠栓对溃疡性结肠炎血管新生和炎症交互作用的调控机制

溃疡性结肠炎（UC）以反复发作的结肠粘膜慢性炎症和溃疡为特点，有很高的癌变风险。UC的发病机制尚不完全明确，但已证实病理性血管生成是导致UC发病的关键病机。血管生成因子的差异调节可能是导致病理性血管生成的根源，但导致这种差异调节的具体机制尚不完全清楚。我们前期研究发现UC模型中促血管生成因子VEGF165a和抑血管生成因子VEGF121表达失衡。清肠栓可纠正该失衡，改善并修复结肠粘膜微血管病变。研究发现VEGF165b可抑制VEGF165a激活VEGFR1信号通路进而抑制血管生成。本项目拟观察VEGF165a/VEGF165b在UC模型中的表达变化，同时观察清肠栓对VEGF165a/VEGF165b-VEGFR1-STAT3通路的调节作用，明确干预该通路能否作为治疗UC的新靶标，进而深入认识血管生成与炎症的内在关系，为中医理论“行血则便脓自愈”提供科学依据，对有效防治UC疾病具有重要意义。

Ulcerative colitis (UC) is characterized by recurrent chronic inflammation and ulceration of the colonic mucosa, which has a high risk of canceration. The pathogenesis of UC is not completely clear. However, it has been proved that angiogenesis is an important part of the pathogenesis of UC. Differential regulation of angiogenesis-related factors may be the cause of pathological angiogenesis. However, the specific mechanism leading to this difference regulation is not yet fully clear. Our previous studies found that the expression of VEGF165a/VEGF121 was imbalanced in UC model. Qingchang suppository can correct the imbalance and improve and repair the microangiopathy of colonic mucosa. Recent studies have shown that VEGF165b inhibits angiogenesis by inhibiting the activation of receptor VEGFR1 signaling pathway by VEGF165a. This project intends to observe the changes of the expression of VEGF165a/VEGF165b in UC model, and observe the regulation of Qingchang Suppository on the pathway of VEGF165a/VEGF165b-VEGFR1-STAT3, so as to clarify whether interventional pathway can be used as a new target for the treatment of UC, and to further understand the internal relationship between angiogenesis and inflammation, so as to provide a scientific basis for the theory of TCM that "blood is expelled and pus heals itself", which has important guiding significance for the effective prevention and treatment of UC.