胃痞消对胃癌前病变Wnt相关信号通路的影响及胃粘膜代谢组学研究

Gastric precancerous lesions (PLGC) can develope to gastric cancer, blocking or reversing the development of PLGC is an effective measure to reduce the incidence of stomach cancer. The finding of gastric adult stem cell marker Lgr5 points out the right direction for PLGC study. The event of movement of gastric mucosa Lgr5+ cells out of "stem cell niche" and event of mucosal angiogenesis accompanied by PLGC, Wnt、Wnt-DLL4/Notch signaling pathway coordination and balance have a major impact on the above events. At the same time, the PLGC pathogenesis is very complex, small changes in gene and protein will be amplified in the metabolite, thus, its mechanism is yet to be further elucidated, and metabolomics is a good means. Our preliminary studies have shown that: weipixiao can improve PLGC pathology, its preliminary mechanism lies in: regulating the mucosal epithelial proliferation and apoptosis; reducing angiogenesis; improving cell sociality of PLGC mucosa. Based on preliminary studies this study will focuse on: the relationship between event of movement of gastric mucosa Lgr5+ cells out of "stem cell niche" and event of mucosal angiogenesis concerning the above signaling pathways, and further, with a platform of PLGC gastric mucosa metabolomics , through data mining and relevance analysis further to reveal weipixiao mechanism on PLGC intervention, thus to enrich the theoretical connotation of PLGC diagnosis and treatment with TCM intervention.

胃癌前病变（PLGC）有发展为胃癌的风险，阻断或逆转其发展是降低胃癌发生率的有效措施。最近，胃腺底干细胞标志物Lgr5的发现为PLGC研究指明了方向。胃粘膜Lgr5+细胞"离巢" 事件及血管新生事件伴随PLGC病理演化，Wnt、Wnt-DLL4/Notch信号通路协调平衡对以上事件有重要影响。同时，PLGC发病机制十分复杂，其具体机制仍待进一步阐明，由于基因、蛋白的微小变化会在代谢物中得到放大，故代谢组学是良好的研究手段。我们前期研究表明：胃痞消能改善PLGC病理，其初步机制和：调节粘膜上皮增殖、凋亡；减少血管生成；改善粘膜细胞社会性有关。本研究拟在前期研究基础上深入探讨：Lgr5+细胞"离巢"及血管生成事件与以上信号通路的关系，进一步以胃粘膜代谢组学为平台，通过数据挖掘及相关性分析手段揭示胃痞消干预PLGC的深层次机制，丰富中医药辨治PLGC的理论内涵。

目前所有指标已经检测统计完毕，研究成果有2篇以综述形式发表，另3篇已被核心期刊录用待发表。另有4篇投稿至国家学术会议并获优秀论文奖。研究指标从以下四部分展开：.A.胃痞消对胃癌前病变大鼠胃粘膜组织学及超微结构的影响：（1）胃痞消对胃癌前病变大鼠粘膜组织学的影响（2）胃痞消对胃癌前病变大鼠胃粘膜腺上皮主细胞及壁细胞超微结构的影响 （3）胃痞消对胃癌前病变大鼠粘膜微血管的超微结构的影响.B.胃痞消对胃癌前病变大鼠炎性因子的影响 .C .胃痞消对胃癌前病变大鼠上皮组织缺氧耐受及糖酵解的影响.D.胃痞消对胃癌前病变大鼠黏膜腺上皮lgr5+细胞增殖与凋亡的影响