近年研究表明:肝细胞凋亡与网状支架破坏是肝纤维化形成的重要病理机制,抑制肝细胞凋亡及其支架结构破坏是防治肝纤维化的根本措施之一,TNF受体（TNF-R）半胱天冬酶（Caspases）通路是细胞凋亡的分子病理基础,ERK-MMP2途径是网状支架破坏的重要分子病理机制。在既往工作基础上,我们拟以抗纤维化有效中药-扶正化瘀方为对象,首先采用析因设计,动态观察扶正化瘀方影响肝细胞凋亡、网状支架破坏与纤维化之间的关系,继而探讨该方及其扶正与化瘀治法拆方对小鼠体内肝细胞凋亡与网状支架破坏的作用机制与治法特点。随后建立中药影响肝细胞凋亡的药物高内涵分析方法,探讨扶正化瘀方及其拆方对培养小鼠肝细胞TNF-R/Caspase通路信号分子的影响;并将经复方与拆方作用的凋亡肝细胞与原代肝星状细胞共培养,观察该方及其拆方通过抗肝细胞凋亡而影响肝星状细胞活化的作用。该项研究阐明了抗肝纤维化有效中药对肝细胞凋亡与支架破坏的作用机制与治法特点,拓展了抗肝纤维化的治疗新途径与药理研究新领域,为进一步开展中医药逆转肝硬化作用机制的研究奠定基础。

Previous studies have indicated that both hepatocytic apoptosis and hepatic reticular scaffold disruption plays a pivotal role in liver fibrogenesis, in which the pathways of tumor necrosis factor receptor （TNF-R）/Caspases, and extracellular regulated kinase （ERK） -matrix metalloproteinase-2 （MMP-2） makes an important molecular pathogenesis. In this context, preventing both hepatocytic apoptosis and reticular scaffold disruption is an essential strategy in treating liver fibrosis. Based our previous studies, we chose Fuzheng Huayu Recipe as a Chinese medicine for antifibrotic treatment. We designed an experiment with factorial design to observe the relationships between the recipe's dynamic effects on hepatocytic apoptosis, and reticular scaffold disruption and fibrosis, before embarking on the mechanism and combined features of the recipe. We plan to work on a high concentration oriented screening of herbal medicines, studying the recipe and its combined action on TNF-R/Caspase signaling in mice hepatocytes. In addition, we will co-culture the apoptotic hepatocytes treated with the recipe, and its combinationals with primary hepatic stellate cells, to observe the herbal effects on hepatic stellate cells activation through apoptotic hepatocytes. The research will eventually elucidate both the mechanisms and combined features of antifibrotic Chinese medicine in treating hepatocytic apoptosis and reticular scaffold disruption. Hopefully, it will produce a new antifibrotic therapy, allowing more room for antifibrotic pharmaceutical research, and laying a sound foundation for reversing liver cirrhosis with Traditional Chinese Medicine.

国家重点基础发展计划(973计划)课题(2006CB504801):肝硬化“虚损生积”的中医病因学研究，负责人：刘平；国家自然科学基金(30772869): 基于肝细胞凋亡与网状支架破坏探讨抗肝纤维化中药的作用机制与治法特点，负责人：刘成海；上海市重点学科建设项目课题(Y0302):HCSA技术为主研究扶正化瘀方对肝细胞凋亡的作用机制及主要物质基础，负责人：刘成海。