中医指出乳岩、噎膈等肿瘤的发生与情志因素有关，但生物学机制不明确，中药抗肿瘤作用及机制研究也陷入瓶颈，这与现有评价模型缺乏对情志因素的考察有关。基于中医情志致病学说与现代医学心理应激致病理论的一致性，本项目前期研究采用心理应激模拟情志刺激，结果提示应激能促进小鼠肿瘤转移，机制可能与应激激素CORT通过上调CD47-SIRPα介导的“don’t eat me signal”抑制巨噬细胞吞噬功能、形成免疫逃逸有关。为验证该假说，本项目拟基于应激建立的肿瘤易感动物模型与CORT巨噬细胞应激模型，采用小动物活体成像、基因敲除、RNAi和活细胞工作站等技术研究CD47-SIRPα通路在情志应激干预巨噬细胞吞噬功能中的作用。基于以上模型，进一步研究以“益气养阴、疏肝理气”等为治则的中药复方单独或配伍的干预作用及机理。旨在揭示中医情志致病的科学内涵，建立和拓展符合中药抗肿瘤作用特点的药效筛选与评价方法。

In traditional Chinese medicine, the development of cancer is suggested to associate with emotional factor, however its molecular biological mechanism remains unknown. Besides, it is difficult to explain the antitumor effects of traditional Chinese medicines which are effective in clinic. The reason is closely relative to the lack of emotional factor in the animal and cellular models. Our previously studies suggested that emotional stress could increase the metastasis of tumor in restrain mice, which is possibly associated with a molecular biological mechanism that corticosterone (CORT), a stress hormone, inhibits the phagocytosis in macrophages and promotes the tumor immune escape through up-regulating the interaction of CD47-SIRPα, a don’t eat me signal between macrophage and tumor. Therefore, tumor susceptibility model and CORT-induced macrophages stress model are established and the phagocytosis of macrophages and the interaction of CD47-SIRPα are studied by Caliper IVIS Lumina II, knockout mice, RNA Interference and live cell imaging system. Furthermore, the pathogenesis of tumor is determined by H&E and immunohistochemistry, and the expression of gene and protein in CD47-SIRPα pathway are determined by Western Blotting and qRT-PCR. On the basis of the above models, the intervention effect and the mechanism of classical anti-tumor formulas aiming to “Reinforcing Qi and Nourishing Yin”, “Relief liver for smooth Qi” and “Softening hardness to dissipate stagnation” are explored in single or in combination. In summary, we aim to explain the role of emotional factor in classical theory of traditional Chinese medicine by western medicine, and to provide an effective screen and evaluation method for traditional Chinese medicine in treating cancers.