四神丸调控Nemo及NLK/TCF/LET信号泛素化预防慢性溃疡性结肠炎复发的作用机制研究

项目名称： 四神丸调控Nemo及NLK/TCF/LET信号泛素化预防慢性溃疡性结肠炎复发的作用机制研究

项目编号： No.81460679

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 刘端勇

作者单位： 江西中医药大学

项目金额： 48万元

中文摘要： 我们以前的研究，表明四神丸有效治疗溃疡性结肠炎的作用途径可能和P38MAPK信号途径有关，根据四神丸临床可有效预防慢性溃疡性结肠炎复发，且Nemo及NLK/TCF/LET信号泛素化在慢性溃疡性结肠炎发作及其在P38MAPK信号活化过程中发挥了关键性作用，我们拟通过复制慢性复发型溃疡性结肠炎大鼠模型，在验证四神丸预防其复发的有效性基础上，从调控Nemo及NLK/TCF/LET信号泛素化水平的角度，观察四神丸对Nemo及NLK/TCF/LET信号泛素化的核心指标，以及与NF-κB信号活化、P38MAPK信号活化及负性调控Wnt/β-catenin信号的关联性指标进行观察，探索四神丸预防慢性溃疡性结肠炎的可能作用机制。进一步揭示四神丸治疗溃疡性结肠炎并预防其复发的可能作用靶点，并借此探索中医药有效预防溃疡性结肠炎复发的可能作用机制，为探索预防溃疡性结肠炎复发的中药新药研发提供科学的参考。

中文关键词： 溃疡性结肠炎；四神丸；复发；Nemo；泛素化

英文摘要： In our previous study, all results had shown that the effect of SiShen Wan (SSW) effectively treated ulcerative colitis (UC) was realized by regulating P38MAPK signal pathway. In the clinical of UC, SSW effectively prevented the relapse of chronic ulcerative colitis. Many studies have hinted that Nemo and ubiquitination of NLK/TCF/LET signal play a key role in attack of chronic UC and activation of P38MAPK signal. We will verify the effectiveness of SSW on preventing the relapse of chronic UC by the model of chronic and relapsed ulcerative colitis, while effect of SSW on regulating ubiquitination of Nemo and NLK/TCF/LET signal which regulated activation of NF-κB signal and P38MAPK signal, negatively regulated Wnt/β-catenin were observed in the study. Furthermore, the probable mechanisms of SSW treated UC, prevented the relapse of UC were disclosed, and to explore possible mechanism of Chinese medicine effectively prevented ulcerative colitis and provide a scientific reference for research and development of new drugs in Chinese herb prevented the relapse of chronic ulcerative colitis.

英文关键词： Ulcerative colitis;Si Shen Wan;relapse;Nemo;uniquination