中文摘要
围绕"证候病机及其与疾病和方剂的相关性"这一证候研究的重要科学问题，基于肝硬化的气虚血瘀"病"病机与湿热内蕴及肝肾阴虚2个主要"证"病机，采用益气、祛瘀、养阴及清热利湿4首不同功效的古典方剂，进行4种不同因素制备的大鼠肝硬化模型的方效比较，以整体综合药效为判识标准，围绕肝纤维化、肝硬化的病理生物学，应用基因芯片与蛋白质组学技术，探讨有效方剂方证相关的病理生物学基础。结果显示，不同因素制备的同疾病模型具有不同功效方剂的取效的病理基础；益气化瘀相对于"病"病机，作用于疾病治疗的靶标；黄芪汤益气作用机制为提高肝组织HGF的表达、抑制TGF-β1的表达以及肝内细胞转分化（肝星状细胞→肌成纤维样细胞，肝细胞→胆管上皮细胞→肌成纤维样细胞）；而提高肝组织胶原降解活性、促进纤维组织的消解是下瘀血汤祛瘀的关键环节；肝组织炎症病理及肝脏代谢病理变化是构成茵陈蒿汤与一贯煎不同方证的病态学基础，以库普弗细胞为中心的炎症病理及脂肪酸代谢异常是茵陈蒿汤的方证基础，肝实质细胞衰减及蛋白合成功能降低是一贯煎的主要方证病理变化。表明基于临床疾病证候病机的"病-方-效-证"是探索疾病中医辨证论治生物学基础的重要途径。
英文摘要
'syndrome-pathogenesis and the correlation between diseases and formula'are very important scientific theory. based on the main disease pathogenesis of liver fibrosis-qi deficiency and blood stasis, as well as syndrome pathogenesis the patterns of dampness and heat accumulation inside and yin-deficiency of the liver and kidney, We selected 4 classic formula which separately have the effects of nourishing qi, removing blood stasis, nourishing yin and clearing heat and removing dampness to prevent or treat the liver cirrhosis models induce by different factors in rats. Further to compare the efficacy, and explore the base of pathology and physiology by molecular biological techniques such as gene chip and proteome. The results showed that different effective formula vary among the one disease models induced by different factors and pathologic basis. According to the disease pathogensis, tonifing qi and removing blood stasis shoot on the main target of liver fibrosis. The mechanism of tonifing qi of Huang-qi decoction includes to incease the expression of HGF of liver tissue, depresse the expression of TGF-β1, and inhibit transdifferentiation of hepatic cells (HSC→myofibroblast, hepatocyte→cholangiocyte→myofibroblast). However, enhancement of activation of collagen degradation and promotion of fibrolysis are the me
结题摘要
围绕"证候病机及其与疾病和方剂的相关性"这一证候研究的重要科学问题，基于肝硬化的气虚血瘀"病"病机与湿热内蕴及肝肾阴虚2个主要"证"病机，采用益气、祛瘀、养阴及清热利湿4首不同功效的古典方剂，进行4种不同因素制备的大鼠肝硬化模型的方效比较，以整体综合药效为判识标准，围绕肝纤维化、肝硬化的病理生物学，应用基因芯片与蛋白质组学技术，探讨有效方剂方证相关的病理生物学基础。结果显示，不同因素制备的同疾病模型具有不同功效方剂的取效的病理基础；益气化瘀相对于"病"病机，作用于疾病治疗的靶标；黄芪汤益气作用机制为提高肝组织HGF的表达、抑制TGF-β1的表达以及肝内细胞转分化（肝星状细胞→肌成纤维样细胞，肝细胞→胆管上皮细胞→肌成纤维样细胞）；而提高肝组织胶原降解活性、促进纤维组织的消解是下瘀血汤祛瘀的关键环节；肝组织炎症病理及肝脏代谢病理变化是构成茵陈蒿汤与一贯煎不同方证的病态学基础，以库普弗细胞为中心的炎症病理及脂肪酸代谢异常是茵陈蒿汤的方证基础，肝实质细胞衰减及蛋白合成功能降低是一贯煎的主要方证病理变化。表明基于临床疾病证候病机的"病-方-效-证"是探索疾病中医辨证论治生物学基础的重要途径。