苦参-黄连配伍防治结直肠腺瘤癌变的功效物质及作用机制研究

文献报道及课题组研究表明，苦参-黄连配伍常有效用于防治结直肠肿瘤、干预癌前病变，且呈现协同增效特点。基于结直肠腺瘤性息肉是结直肠癌最主要的癌前病变，且符合“湿热毒蕴”的病机特点，本课题提出：苦参-黄连配伍清热化湿解毒，可能通过干预结直肠腺瘤性息肉癌变防治结直肠肿瘤，且具有特定的量效关系。本项目拟在癌毒病机理论指导下，建立结直肠腺瘤癌变模型及功效评价方法，通过体内与体外实验，聚焦“腺瘤-癌”病机演变的关键生物学靶标STAT3、SIRT3，综合运用现代谱学串联技术与多种生物学手段，采用多指标综合指数法结合人工神经网络拟合、选择性定向剔除技术揭示苦参-黄连配伍防治结直肠腺瘤癌变的功效物质。通过开展主要效应成分的ADME研究，多组分PK-PD相关性分析，结合响应曲面分析法与比较代谢组学等策略，探讨苦参-黄连配伍作用机制，为阐释中药配伍机理、抗肿瘤药物创制以及指导结直肠肿瘤防治提供有益探索和依据。

According to the related literatures and the research group’s study, the complex of Sophora flavescens and Coptis chinensis is often used to prevent and treat colorectal tumors and precancerous lesions, and a synergistic effect is observed. Colorectal adenomatous polyps are the most important colorectal precancerous lesions, and they show the pathogenesis characteristics of "dampness heat toxin amassment". Accordingly, we propose that the complex of Sophora flavescens and Coptis chinensis can clear heat-toxin and eliminate dampness, and thus may prevent colorectal cancer by intervening carcinogenesis of colorectal adenomatous polyps, showing a dose dependent effect. This project intends to focus on the key STAT3 and SIRT3 signaling pathways involved in the "adenoma-carcinogenesis" pathology, and establish the model of colorectal precancerous lesions and efficacy evaluation methods through in vivo and in vitro experiments, under the guidance of the theory of cancer toxin pathogenesis. In addition, by employing modern spectroscopy tandem technology with a variety of biological methods, as well as multi-index comprehensive index methods combined with artificial neural network fitting and selective directional rejection technology , we can find the effective substances of the complex of Sophora Flavescens-Coptis chinensis in preventing and treating carcinogenesis of colorectal adenomatous polyps. Through ADME study, multi-component PK-PD correlation analysis, combined with Response Surface Methodology and comparative metabolomics on the main effective components, the compatibility mechanism of Sophora flavescens-Coptis chinensis will be investigated. In short, this project will provide a powerful basis for explaining the compatibility mechanism of traditional Chinese medicines, discovering antitumor drugs, and directing the prevention and treatment of colorectal tumors.