“形气神同调”视角下痛泻要方抑制精神压力诱导的TSC22D3过表达调复Th1/Tc1免疫应答阻延结肠癌演进研究

精神心理因素致免疫功能异常在肿瘤的发生发展中扮演了关键角色。最新研究发现，精神压力诱导TSC22D3过表达、抑制MHC-I/II—Th1/Tc1免疫应答从而促结肠癌演进，这不仅与“木郁土虚”的病机表征关联，更契合了“形气神一体”的中医认识。现有研究确证痛泻要方可阻延结肠癌进程，其干预精神相关性肠病的优势效应提示抑木调“神”亦是阻延结肠癌演进的关键一环。据此提出研究假说：抑木扶土的痛泻要方可能通过抑制TSC22D3过表达、调复MHC-I/II—Th1/Tc1免疫应答的肠外精神应激干预效应，阻延了结肠癌进展。本项目拟构建结肠癌小鼠社会失败应激模型，利用原代肿瘤细胞培养、基因转染等技术，明确痛泻要方阻延结肠癌演进的肠外效应及靶点，揭示中医整体观的生物学内涵，为“形气神同调”治则治法提供实证依据，丰富肿瘤中医论治体系。

Psychological distress plays a key role in tumor progression by damaging the immune function. The latest research found that stress-induced TSC22D3 upregulation dampens MHC-I/II—Th1/Tc1 immune responses and promotes the progression of colon cancer, verifying the validity of the “hepatic stagnation causing splenic deficiency” pathogenesis, as well as the physiological and pathological understanding of “Integration of Form, Qi and Spirit” in TCM. Existing studies have confirmed that Tongxieyaofang delays the progression of colon cancer and alleviates psychiatric-associated bowel disease, suggesting that smoothing liver qi and regulating spirit is a key link in slowing down the progression of colon cancer. A hypothesis is thus proposed: Tongxieyaofang may delay the progression of colon cancer by downregulating the stress-induced over-expressed TSC22D3 and recovering MHC-I/II—Th1/Tc1 immune responses. This project will establish a social defeat (depression)& colon cancer animal model, use primary cell culture, gene transfection and other technologies to clarify mental intervention effects and targets out of colons of Tongxieyaofang in delaying the progression of colon cancer. The project will reveal the biological connotation of TCM Holistic Conception, providing empirical basis for the rule of “Simultaneous Regulation of Form, Qi and Spirit” and enriching the TCM treatment system for tumors.