《金匮要略》“见肝之病，知肝传脾，当先实脾”的实证研究

In the JINGUI Explanatory.“ See the liver disease, liver spleen known biography, leading the spleen ” is not only the concrete embodiment of the treating pre-disease of ZHANG Zhong-jing,but also the important therapeutic principles of traditional Chinese medicine treatment on liver disease.the methods of “consolidating spleen firstwhile liver is affected” is widespread used in Liver disease in China.Although there are many correlational research on liver stangation and spleen defieiency.But a lot of studies now focused on correlational mechanism of pathological state of comorbidity of liver and spleen.the dynamic and objective experimentational bases and biological mechanism of "see the liver disease, liver spleen known biography, leading the spleen" have not yet been revealed.with a view to two key words of “affecting” and “leading” in “liver spleen known biography, leading the spleen” This project by making Liver-stagnation model and Combinational model of Liver-stagnation and chronic liver injure in rats, From the gastrointestinal mucosa, gastrointestinal motility, liver function ,HPA axis,brain-gut peptide,histopathological aspects, to observe the above indexes change in rats through following groups:sini powder group,liujunzi decoction group, chaishaoliujunzi decoction 1 group, chaishaoliujunzi decoction 2 group , chaishaoliujunzi decoction 3 group. Preliminary study on” See the liver disease, liver spleen known biography” biological mechanism. It is a beneficial and sciencial explore to explain the theory of “treating pre-disease” of ZHANG Zhong-jing and to rich the theory of traditional chinese medicine to prevent the liver disease.

《金匮要略》“见肝之病，知肝传脾，当先实脾”是张仲景治未病理论的具体体现，也是中医药治疗肝病的重要治法，肝病实脾法广泛应用于临床防治肝病。虽肝郁脾虚相关研究较多，但目前多集中于肝脾同病的病理状态下相关机制研究。“知肝传脾”、“当先实脾”的动态客观实验证据及生物学机制尚未揭示。本项目着眼于“知肝传脾”的“传”和“当先实脾”的“先”字，复制肝郁大鼠模型、肝郁叠加慢性肝损伤大鼠模型，从胃肠黏膜、胃肠运动功能、肝功能、HPA轴、脑肠肽、组织病理等方面，观察比较正常组、模型组、四逆散组(疏肝)、六君子汤组（健脾）、柴芍六君子汤甲组（疏肝健脾）、柴芍六君子汤乙组（先给四逆散，后给柴芍六君子汤）、柴芍六君子汤丙组（先给六君子汤，后给柴芍六君子汤）大鼠上述指标变化，探讨“见肝之病，知肝传脾，当先实脾”的客观证据及生物学机制，为诠释张仲景治未病理论，丰富与发展中医药防治慢性肝病的治则治法进行有益的科学探索。

《金匮要略》“见肝之病，知肝传脾，当先实脾”是张仲景治未病理论的具体体现，也是中医药治疗肝病的重要治法，肝病实脾法广泛应用于临床防治肝病。虽肝郁脾虚相关研究较多，但目前多集中于肝脾同病的病理状态下相关机制研究。“知肝传脾”、“当先实脾”的动态客观实验证据及生物学机制尚未揭示。本项目着眼于“知肝传脾”的“传”和“当先实脾”的“先”字，复制肝郁大鼠模型、肝郁叠加慢性肝损伤大鼠模型，从胃肠黏膜、胃肠运动功能、肝功能、HPA轴、脑肠肽、组织病理等方面，观察比较正常组、模型组、四逆散组（疏肝）、六君子汤组（健脾）、柴芍六君子汤甲组（疏肝健脾）、柴芍六君子汤乙组（先给四逆散，后给柴芍六君子汤）、柴芍六君子汤丙组（先给六君子汤，后给柴芍六君子汤）大鼠上述指标变化，探讨“见肝之病，知肝传脾，当先实脾”的客观证据及生物学机制，为诠释张仲景治未病理论，丰富与发展中医药防治慢性肝病的治则治法进行有益的科学探索。.本项目研究严格按照计划基本顺利完成。研究结果显示：“见肝之病，知肝传脾，当先实脾”具有客观性，其在肝郁叠加慢性肝损伤大鼠模型中得到了更好的体现。六君子汤组（健脾）、柴芍六君子汤组（疏肝健脾）及六君子汤＋柴芍六君子汤组（先健脾，后疏肝健脾）的治疗有效改善肝郁叠加慢性肝损伤大鼠模型的肝功能及胃肠动力，可能是从“健脾”作用切入，通过下丘脑-垂体-肾上腺轴及脑肠肽Ghrelin、SP、VIP等信号通路，提高胃肠蠕动，影响胃酸分泌，保护胃黏膜，参与情绪、心理的调节并调节下丘脑的功能及末梢神经系统的神经传递，从而使情志条畅而肝舒达使肝病得到缓解；同时另一方面可能是通过调控Bax、Bcl-2等凋亡基因/蛋白，从而直接改善肝细胞凋亡情况，而使肝损伤得到纠正。结合各项指标，各治疗组中先用六君子汤后用柴芍六君子汤方的柴芍六君子汤丙组治疗效果最佳，恰是体现了“见肝之病，当先实脾”之理。