山莨菪碱和新斯的明联合治疗溃疡性结肠炎的作用和机制研究

Ulcerative Colitis (UC) is a chronic non-specific inflammatory bowel disease, which often recurs and persists. The immune dysfunction and intestinal flora imbalance play an important role in the pathogenesis of UC. So far, the treatment of UC is still a big challenge for clinicians. Long-term researches from our laboratory have indicated that the combination of anisodamine and neostigmine has significant anti-inflammatory and immunosuppressive effects. In an explored experiment, we found neoscopolamine is markedly effective on the treatment of UC induced by DSS in mice. In order to elucidate its mechanism, this project will be divided into the following parts: 1) to clarify the therapeutic effect of neoscopolamine on UC; 2) to elucidate the role of anti-inflammatory and flora regulation on the pathophysiological mechanism of neoscopolamine in the treatment of UC, and further more to explore the relationship between anti-inflammatory or flora regulation and autophagy; 3) to confirm α7nAChR activation mediating the protective effect of neoscopolamine on UC. This project will provide new drugs and strategies for treatment of UC.

溃疡性结肠炎(Ulcerative Colitis，UC)是一种慢性非特异性炎症性肠病，常反复发作，迁延难愈。在UC的病理生理机制中免疫功能紊乱与肠道菌群失调起到重要作用。目前，UC的治疗仍是困扰临床医生的难题之一。本实验室长期的研究发现山莨菪碱和新斯的明联合（新斯莨菪碱）具有显著的抗炎和免疫抑制作用。我们将其探索性地用于治疗DSS诱导的小鼠UC，结果发现新斯莨菪碱对UC具有很好的治疗作用。为了进一步深入阐明其机制，本项目拟从如下几方面展开研究：1）明确新斯莨菪碱对溃疡性结肠炎的治疗作用；2）阐明新斯莨菪碱治疗UC的病理生理机制，即抗炎作用和菌群调节作用；并进一步探讨二者与自噬的关系，3）确定新斯莨菪碱治疗UC的分子靶点，即激活alpha7nAChR。该项目的完成，将会为UC开发新的治疗药物和治疗策略。

溃疡性结肠炎（UC）是一种慢性炎症性疾病，常反复发作，迁延难愈，目前尚无效果显著的治疗手段和治疗药物。在本项目执行过程过，申请人根据前期研究基础，着重围绕新斯的明/山莨菪碱联合（新斯莨菪碱）对UC的治疗作用，新斯莨菪碱治疗 UC 的病理生理机制以及新斯莨菪碱治疗UC的分子靶点展开研究，发现，1）新斯莨菪碱对DSS诱导的小鼠结肠炎有很好的治疗作用；2）新斯莨菪碱能够增强结肠炎小鼠肠道自噬水平；3）新斯莨菪碱能够通过促进肠道自噬抑制炎症反应介导其对小鼠结肠炎的保护作用；4）新斯莨菪碱可以调节结肠炎小鼠的肠道菌群；5）新斯莨菪碱通过激活α7 尼古丁乙酰胆碱受体（α7nAChR）发挥对结肠炎的治疗作用。在该项目的资助下，发表论文1篇，修回1篇，申请国家发明专利1项，培养硕士研究生1名。