铁皮石斛多糖基于NRF2/HO-1通路调控巨噬细胞极性预防胃癌前病变脾虚证的机制研究

脾虚造成巨噬细胞功能下降，是胃癌前病变的发病基础。巨噬细胞是免疫微环境的重要组成部分，激活NRF2/HO-1会促使巨噬细胞向M2型发展，发挥抗炎的作用。已证实铁皮石斛多糖（DOP）激活NRF2/HO-1通路，高表达下游抗氧化酶HO-1，从而预防胃癌前病变。但是否会对巨噬细胞的分型和极化产生影响，目前还不明确。进而提出假说：DOP通过NRF2/HO-1通路，提高HO-1表达后作用于巨噬细胞的分型和极性表达，从而预防胃癌前病变脾虚证的恶化。利用RT-PCR、WB、流式细胞仪、细胞共培养等技术，明确DOP对巨噬细胞表型、胃癌癌前MC细胞的影响，探索巨噬细胞细胞与MC细胞共培养的互作关系，阐释DOP基于NRF2/HO-1通路平衡M1/M2型巨噬细胞，改善胃癌前病变脾虚证的科学内涵，为探讨多糖类成分调控免疫微环境防治肿瘤的分子机制提供新视角。

Spleen deficiency causes the decline of macrophage function, which is the basis of precancerous lesions of gastric cancer. Macrophages are an important component of the immune microenvironment, and M1/M2 type macrophages can produce multiple effects of pro-inflammatory /anti-inflammatory, anti-tumor/ promoting cancer. Activation of NRF2/HO-1 will promote the macrophages towards to M2 type, and play an anti-inflammatory role. We confirmed that the Dendrobium officinale polysaccharide (DOP) could activate the Nrf-2/HO-1 pathway,and increase the expression of antioxidant enzymes HO-1, in order to prevent gastric precancerous lesions. However, it is not clear whether it will affect the classification and polarization of macrophages. We put forward the hypothesis that DOP will prevent the progression of precancerous lesions of gastric cancer by balancing M1/M2 macrophages though NRF2/HO-1 pathway. Using RT-PCR, WB, flow cytometry, co-culture technique to clear the effect of DOP on macrophage phenotype and gastric precancerous lesions MC cells, and to explore the interaction between macrophages and MC cells.In the end,DOP through activating NRF2/HO-1 pathway to balance macrophages’M1/M2 type,and clarify the scientific connotation of spleen deficiency in process of good gastric precancerous lesion. To provide a new perspective that the molecular mechanism of polysaccharide composition in regulating of immune microenvironment for tumor prevention and treatment.