疏肝健脾方对病证结合的乳腺癌模型髓系抑制性细胞-NKT细胞免疫重塑的调控研究

抑郁焦虑负性情绪障碍是促进肿瘤发生、发展的重要因素，但既往缺乏关注和机制探讨。近期研究显示：髓系抑制性细胞（MDSC）所诱导的免疫抑制与其作用机制密切相关，而JAK/ STATs-NO/ROS信号传导途径介导的CD8+T细胞凋亡和NKT细胞促分化作用是MDSC诱导免疫抑制的关键。抑郁焦虑属于中医学"肝郁"范畴，肝郁脾虚是最常见的临床证型，前期研究显示：疏肝健脾方可以通过抑制病证结合的肝郁脾虚小鼠乳腺癌4T1模型体内MDSC的扩增作用，从而逆转CD8+T细胞凋亡。本课题在前期基础上，利用体内及体外共培养研究平台，运用流式细胞术、小动物活体成像、CFSE法等技术，动态观察抑郁焦虑负性情绪障碍对乳腺癌发生、发展的影响及疏肝健脾方的干预作用，从调控JAK/STATs -NO/ROS信号途径介导的MDSC-NKT细胞免疫重塑的新视角，探讨中药逆转乳腺癌免疫逃逸的作用及分子机制,丰富中医情志学说.

Anxiety and depression of psychological stress are the main causative factors of tumorigenesis and metastasis, which have a severe influence on the life quality and life span of cancer patients. Recent studies have shown that immune suppression induced by Myeloid-derived Suppression Cell (MDSC) plays an important role in the process, and the key mechanisms are probably related with CD8+ T cell apoptosis and NKT differentiation mediated by JAK/ STATs- NO/ROS signal transduction pathway. In traditional Chinese medicine, depression and anxiety belong to liver qi depression, and the pattern of liver depression and spleen deficiency is most commonly seen in the clinic. Our prior study indicated that LSSFF could reverse CD8+ T cell apoptosis through inhibiting the amplification of MDSC in the disease-pattern mouse 4T1 breast cancer model. On basis of this, we design this study by using flow cytometry, in vivo imaging technology in Small Animal, real-time PCR and CFSE assay to dynamically observe the influence of anxiety and depression on breast cancer animal model and the intervention of LSSFF, and further investigate the effect and mechanism of Chinese medicine on the reversing immune escape in breast cancer body from a new viewpoint: whether it is through regulating the immune remodeling of MDSC and NKT mediated by JAK/ STATs- NO/ROS signal transduction pathway? The study will provide scientific evidence for the application of liver-soothing and spleen-fortifying principle in cancer prevention and treatment guided by emotion-thought theory of TCM.