中文摘要
胃肠粘膜损伤修复是益气健脾中药作用机制之一,上皮细胞迁移是胃肠粘膜损伤修复的重要环节;申请人前两课题发现益气健脾中药能促进小肠上皮细胞迁移,作用机制与其影响多胺调控信号通路有关,可通过促进胞内钙库释放Ca2+和胞外Ca2+内流两途径(后者作用更明显),提高细胞Ca2+水平而促进细胞迁移;但若无Ca2+内流则益气健脾中药作用明显减弱,表明对Ca2+调控是关键指标,本课题进一步围绕多胺信号通路Ca2+调控过程,观察益气健脾中药促进细胞迁移的作用机制:对Ca2+内流驱动力、蛋白复合体调控(STIM1/TRPC1、STIM1/STIM2、Rac1/PLC-r1、RhoA/TRPC1、Cav1/TRPC1)、特定蛋白抑制后的影响等,以多胺和Ca2+调控为关键指标,研究益气健脾中药胃肠粘膜保护机制,对阐述益气健脾中药治疗脾胃病和“脾为之卫”的科学内涵有重要意义,也为益气健脾创新药物研究提供基础。
英文摘要
The effect on gastrointestinal mucosal repair after wounding is one of the mechanisms of Yi-qi-jian-pi herbs. Migration of epithelial cells is important for the repair of gastrointestinal mucosal injuries. Our previous two researches indicated that Yi-qi-jian-pi herbs could promote cell migration, of which the mechanism is related to its effect on polyamine-mediated signal ways. Yi-qi-jian-pi herbs could improve cytosolic free calcium concentration ([Ca2+] cyt), by increasing Ca2+ release from intracellular stores and extracellular Ca2+ influx through Ca2+-permeable ion channels, which play an important role in the stimulation of cell migration after wounding, whereas extracellular Ca2+ influx is more important. The promoting effects of Yi-qi-jian-pi herbs attenuated apparently in absence of extracellular Ca2+, which suggested regulatory effects of Ca2+ are key points. This study will be undertaken to further investigate the mechanism of promoting effect of Yi-qi-jian-pi herbs on intestinal epithelial cell migration, focusing on calcium regulation in polyamines-dependent signal way. Key targets such as Ca2+ influx driving force, regulating effect of protein complexes (STIM1/TRPC1, STIM1/STIM2, Rac1/PLC-r1, RhoA/TRPC1, Cav1/TRPC1) and influence of specific protein inhibitor will be determined to study the mechanism of Yi-qi-jian-pi herbs protecting gastrointestinal mucosa, which will elucidate the scientific connotation of the therapeutic effects of Yi-qi-jian-pi herbs on Spleen and Stomach disease and the conception “spleen as the defense of five-zang viscera and six-fu organs” and also provide foundation to the researches of innovative drug of yi-qi-jian-pi herbs.
