“病-方(效)-证”的研究实践与创新发展(一)——黄芪汤治疗肝硬化的方证病理学基础探析

Research practice and innovative development of“disease-formula(effect)-syndrome”(Ⅰ)——Analysis on pathological basis of formula and syndrome of Huangqi Decoction in treatment of liver cirrhosis

围绕“病证相关,方证相应”的学科重要问题,笔者曾提出“病-证-效”研究思路,近20年的研究实践显示,这应是实现中医学传承与创新的有效途径之一。充分利用现代医学及生命科学的研究成果,研究证候病机与“疾病和方剂”的相关性,明晰疾病的方证病理学基础,是证候研究的关键科学问题。作者基于前期研究结果,解析了益气补虚黄芪汤抗肝纤维化的作用特点为抑制肝星状细胞(HSCs)向肌成纤维细胞转分化,抑制肝祖细胞(HPCs)向胆管上皮细胞转分化,以及调节胆汁酸代谢异常等;从有效方剂的效应基础演绎了肝硬化气虚病机的关键病理学基础可能与HSCs和HPCs的异常转分化(细胞形质及功能变化)及胆汁酸代谢异常有关,为“病-方(效)-证”结合探索疾病中医方证病机的病理生物学基础、发现古典方剂新用途研究提供了发展思路。

Focusing on the important issues of the discipline of“disease syndrome correlation,formula syndrome correspondence”,the research idea of“disease-syndrome-effect”was once proposed.Nearly two decades of research practice shows that this should be one of the effective ways to realize the inheritance and innovation of traditional Chinese medicine.Making full use of the research results of modern medicine and life science,studying the correlation between syndrome pathogenesis and“disease and formula”,and clarifying the pathological basis of disease formula and syndrome are the key scientific issues in syndrome research.Based on the results of previous studies,the authors analyzed the anti-liver fibrosis effects of Yiqi Buxu Huangqi Decoction,which are characterized by inhibiting the transdifferentiation of hepatic stellate cells(HSCs)into myofibroblasts,and hepatic progenitor cells(HPCs)into bile duct epithelial cells,as well as regulating the abnormal metabolism of bile acids.The key pathological basis of Qi deficiency pathogenesis of liver cirrhosis deduced from the effect basis of effective formulas may be related to the abnormal transdifferentiation of HSCs and HPCs(changes of cell shape and function)and abnormal bile acid metabolism.It provides a development idea for the combination of“disease-formula(effect)-syndrome”to explore the pathobiological basis of the pathogenesis of traditional Chinese medicine formulas and syndromes,and to discover the new uses of classical formulas.