藏药“甲嘎松汤”调节Nrf2/Bach1-ARE-抗氧化酶通路以抗氧化保肝的研究

项目名称： 藏药“甲嘎松汤”调节Nrf2/Bach1-ARE-抗氧化酶通路以抗氧化保肝的研究

项目编号： No.81202997

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 熊天琴

作者单位： 广州中医药大学

项目金额： 23万元

中文摘要： 氧化应激是肝损害性疾病的重要病理特征，但临床缺乏有效的抗氧化药物。Nrf2/Bach1-ARE-抗氧化酶通路被公认是关键的内源性抗氧化应激通路，调控Nrf2和Bach1的平衡是防治肝损伤性疾病的有效手段。前期研究显示藏方"甲嘎松汤"通过抗氧化而保肝，其作用与Nrf2、Bch1有关，但其机制还不清楚。我们提出"甲嘎松汤" 可能通过调控Nrf2/Bach1的平衡而控制抗氧化酶基因的适度表达发挥抗氧化保肝作用的科学假说。本课题在保证制剂成分稳定的前提下，拟采用免疫荧光、Western blot、RT-PCR等方法，研究RNA干扰Nrf2和/或Bach1表达对"甲嘎松汤"保护肝细胞效应的影响；利用体外细胞和整体动物模型，动态地研究甲嘎松汤调控Nrf2和Bach1在胞核和胞浆中表达、移位、调节抗氧化酶的时间规律，以阐明"甲嘎松汤"保肝机制，为临床适应症选择提供实验依据，为抗氧化保肝药物筛选提供基础。

中文关键词： 甲嘎松汤；抗氧化；保肝；Nrf2/Bach1；基因沉默

英文摘要： Oxidative stress is the important pathologic feature of Liver injury diseases , but the effective clinical drug is in lacking. The Nrf2 / Bach1-ARE-antioxidase signal pathway is recognized as the key endogenous antioxidant stress pathways, so it is an effective means of preventing and curing the injured liver to balance Nrf2 and Bach1.The previous researches show that Traditional Tibetan medicine JiaGaSong Tang can protect the injured liver by antioxidation , which relates to Nrf2 and Bch1 ,but the mechanism is not clear. So we put forward a scientific hypothesis that JiaGaSong Tang may antagonise oxidative stress to protect liver in regulating the balance of Nrf2 and Bach1 to control the moderate expression of antioxidant enzyme gene. In this project, by using immune fluorescence, Western blot, RT-PCR and other methods ,we study the effect of RNA interfere Nrf2 or Bach1 on the hepatoprotective effect of JiaGaSong Tang. To clarify the protective mechanism of JiaGaSong Tang, in rat models and cell models ,we study the regulation effect of JiaGaSong Tang on the time regularity of Nrf2 and Bach1 , which including the expression in the nuclei and cytoplasm , nuclear shifting, and regulation antioxidant enzymes. This study will provide the experimental basis for choosing clinical indications and screening drugs of an

英文关键词： Jiagasong tang(JGST)；Anti-oxidation；Liver protection；Nrf2/Bach1；siRNA