从嗅素蛋白4介导的NOD1/CDX2通路探讨萎胃颗粒干预胃黏膜肠上皮化生的作用机制

肠上皮化生（IM）是常见的胃黏膜病变，属中医胃痞病范畴，治疗困难，发病率高，是胃黏膜病理恶性转变的关键阶段。转录因子CDX2可调控肠道特异基因的表达，在IM中起关键作用。据报道胞内识别受体NOD1调控CDX2，诱导IM发生。课题组生物信息学发现嗅素蛋白4（OLFM4）表达升高是IM发生的重要启动因素，同时文献报道OLFM4能上调NOD1，诱导炎性因子表达。萎胃颗粒可以改善IM及胃黏膜慢性炎症，预实验发现萎胃颗粒可下调CDX2及肠道标志物。因此我们推测：OLFM4通过NOD1刺激CDX2表达，推动IM进展。萎胃颗粒可下调OLFM4及NOD1，抑制CDX2表达，逐步阻断IM的发展。本项目拟采用慢病毒转染、荧光素酶检测技术、染色质免疫沉淀等手段，阐明OLFM4介导的NOD1/CDX2在IM中的作用，以及萎胃颗粒抑制OLFM4介导的NOD1/CDX2减轻IM的作用。

Intestinal metaplasia (IM) is a common gastric mucosal disease, which belongs to the “Weipi” in traditional Chinese medicine. It is difficult to treat and has a high incidence. It is a key stage of malignant transformation of gastric mucosal pathology. The transcription factor CDX2 can regulate the expression of intestinal-specific genes and plays a key role in IM. It is reported that the intracellular recognition receptor NOD1 regulates CDX2 and induces the occurrence of IM. The bioinformatics research team found that the increased expression of olfactory protein 4 (OLFM4) is an important initiating factor for the occurrence of IM. It is reported in the literature that OLFM4 can up-regulate NOD1 and induce the expression of inflammatory factors. Weiwei granules can improve IM and chronic inflammation of gastric mucosa. Preliminary experiments have found that Weiwei granules can down-regulate CDX2 and intestinal markers. Therefore, we speculate: OLFM4 stimulates the expression of CDX2 through NOD1 and promotes the progress of IM. Weiwei Granules can down-regulate OLFM4 and NOD1, inhibit the expression of CDX2, and gradually block the development of IM. This project intends to use lentiviral transfection, luciferase detection technology, chromatin immunoprecipitation and other methods to clarify the role of OLFM4-mediated NOD1/CDX2 in IM, and Weiwei Granules inhibit OLFM4-mediated NOD1/CDX2 to reduce IM.