黄芪甲苷逆转直肠Cajal细胞表达在梗阻性排便综合征治疗中的机制研究

Gastrointestinal interstitial cells of Cajal (ICC) is closely related to the pathogenesis of obstructed defecation syndrome (ODS). At present we found that the number of ICC in all rectal tissue layers significantly decreased in ODS patients and integrative medicine therapy such as Huangqitang could significantly improve the curative effect of ODS. Further study showed: the number of ICC in the group of taking Astragaloside IV was significantly increased in ODS patients compared with that of control group. Therefore, our team intends to study: the effect of Astragaloside IV on expression of rectal ICC in ODS patients; the relationship between Astragaloside IV reversing rectal ICC in ODS and SCF /c-kit signal pathway; the correlation in ODS patients between the number of rectal ICC and its efficacy. This study will elucidate the potential mechanism of Astragaloside IV for treating ODS, thus reveal the role of ICC in the pathogenesis of ODS, and provide scientific supports for traditional Chinese medicine in the treatment of ODS.

胃肠间质Cajal细胞（ICC）与梗阻性排便综合征(ODS)的发病机制关系密切。前期研究已发现：ODS患者直肠不同层次的ICC数量均明显下降；黄芪汤等中西医结合治疗可以明显提高ODS的疗效。进一步研究发现：服用黄芪甲苷的ODS患者直肠的ICC数量较不服用黄芪甲苷者明显增加。由此拟研究：黄芪甲苷对ODS患者直肠组织ICC表达的影响；黄芪甲苷逆转ODS直肠ICC与SCF/c-kit信号通路的关系；分析ODS直肠组织ICC数量是否与ODS的临床疗效存在相关性。通过本研究，我们将阐明黄芪甲苷治疗ODS的作用机制，从而揭示ICC在ODS发病机制中的作用，同时为中医药治疗ODS提供现代科学依据。

胃肠间质Cajal细胞（ICC）与便秘的发病机制关系密切。本项目利用临床试验、动物造模、16s rDNA、代谢组测序、细胞及分子生物学实验，阐明便秘患者的直肠组织ICC变化规律、以及临床疗效与ICC的关系，并从“肠道菌群-代谢产物-宿主”的角度出发解析黄芪甲苷在便秘治疗中的作用途径和机制。结果发现：便秘患者的直肠ICC细胞数目下降，ICC是便秘临床疗效的独立预测因素；黄芪甲苷可显著改善便秘小鼠的排便和结肠动力功能；便秘小鼠的粪便微生物群的细菌多样性降低，黄芪甲苷治疗后粪便微生物群的细菌多样性有所增加；在动物和细胞水平研究发现肠道菌群可通过增加丁酸盐来激活AKT/NF-kappa B信号通路促进ICC增殖以改善便秘。本项目首次将中药黄芪治疗便秘的研究引向单分子水平，对临床具有重要的指导意义。