大柴胡汤“方-证要素对应”及其调节非酒精性脂肪性肝病“肠-肝轴”多靶点的相关分析

Da Chai Hu decoction is an effective prescription in treating non-alcoholic fatty liver disease (NAFLD). For the unclear relations between prescription compositions, compatibility law and effect targets, improving therapeutic efficiency and application of reasonable modification in NAFLD have been limited.In the previous studies, we have proposed the prescription compatibility principle of “correspondence between syndrome and formula factors”. Based on this, we have found that the composition principle of Da Chai Hu decoction and the gut-liver axis pathogenesis in NAFLD are strikingly similar through network correlation analysis. Therefore, we raise the hypotheses of “syndrome factors – formula factors –effect targets” to explore their related essence. We intend to investigate the mechanism of Da Chai Hu decoction in regulating effect targets of NAFLD via gut-liver axis by decoction through high-fat diet fed SD rats model. With these purposes, we perform to use morphology, immunology, pathology, molecular biology, FITC-LPS fluorescent labeling and other technical measures. In addition, mathematical statistical methods will be used to analysis the correlation. The study has the following meanings: ① In order to provide experimental basis for illustrating the compatible regularity and mechanism of “treat with gut and liver together” of Da Chai Hu decoction theoretically. ② To provide the best drug combination regimens for prevention and treatment of NAFLD practically. ③ To establish the research pattern of the combination of principle-method-recipe-medicine in the research methods of TCM compound.

大柴胡汤是临床治疗非酒精性脂肪性肝病（NAFLD）的有效方剂，但因对其方剂结构、配伍规律与疗效作用靶点的关系尚不十分清楚，从而影响了该方临床治疗本病疗效的进一步提高及化裁应用。本团队在以往研究提出“方-证要素对应”组方原则的基础上，通过网络相关分析发现了大柴胡汤“肠肝同治”组方原理与NAFLD“肠-肝轴”发病学说的相似之处，为探讨两者相关实质提出“方剂要素-证候要素-效应靶点”相关假说。拟采用形态学、免疫学、病理学、分子生物学、FITC-LPS荧光标示等技术，通过动物模型拆方观察大柴胡汤调节NAFLD“肠-肝轴”作用靶点的机制，并运用数理统计学方法进行相关分析。研究具有以下意义：①在理论上，为阐明大柴胡汤“肠肝同治”的配伍规律及其作用机制提供科学实验依据。②在实践上，为临床防治NAFLD提供最佳药物组合方案。③在中药复方研究方法上，建立理-法-方-药-作用靶点紧密结合的研究模式。

本项目通过动物模型拆方观察大柴胡汤调节非酒精性脂肪性肝病（NAFLD）“肠-肝轴”作用靶点的机制，并运用数理统计学方法进行了相关分析，印证了“方剂要素-证候要素-效应靶点”相关及方剂要素之间存在配伍效应的假说。研究表明，大柴胡汤“疏利肝胆组”方剂要素（柴胡、黄芩、白芍）对应“肝胆疏泄失职”证候要素，具有调节肝免疫功能；“健脾化痰和胃组”方剂要素（大枣、半夏、生姜）对应“脾虚痰湿中阻”证候要素，具有保护胃肠黏膜屏障功能；“通腑泄浊组”方剂要素（大黄、枳实）对应“大肠浊热”证候要素，具有清除肠道有害菌群功效。从“方-证要素对应”角度对大柴胡汤进行组方分析，为大柴胡汤的临床化裁应用及扩大应用范围提供了新的思路。部分揭示了大柴胡汤各“方剂要素”作用于“肠-肝轴”的优势靶点以及各“方剂要素”调节“肠-肝轴”靶点的相关性，为开展中药复方“多靶点”作用机制研究提供了思路和方法。