基于SIRT1-AMPK信号系统探讨酒精性脂肪肝能量代谢变化与分子调节机制及葛花解酒涤脂汤干预研究

酒精性脂肪肝(AFLD)是酒精性肝病进行性发展的重要起始病理阶段，尚无有效的治疗措施。SIRT1-AMPK信号对细胞能量和细胞氧化还原状态具有重要调节作用，且二者在AFLD中的作用已得到肯定。肝脏作为机体储存能量和调节代谢的重要器官，其代谢与能量平衡同机体生命活动密切相关。因此，基于上述研究基础与理论，我们设想肝脏能量代谢及其变化与AFLD发生具有重要相关性，但缺乏文献支持。课题组前期预实验发现，由经方与自拟方临证加减后形成的葛花解酒涤脂汤能够显著改善AFLD小鼠肝脏脂肪变性，其作用显著优于白藜芦醇。本课题拟通过动物体内和体外细胞实验，探讨能量代谢与AFLD发生的相关性、乙醇暴露后AFLD相关microRNAs对SIRT1- AMPK信号表达与活性调节机制及其对能量代谢的影响，进一步阐明AFLD发生的分子机制，同时为发挥中医药在AFLD治疗中的独特优势提供科学的实验室依据。

Alcoholic fatty liver (AFLD) is a major risk factor for advanced liver injuries such as steatohepatitis, fibrosis, and even hepatocellular carcinoma (HCC), which no effective treatment measures.SIRT1 - AMPK signal has an important regulatory role in cellular energy and redox status, and the role of both in AFLD has been sure. Liver is thought as a key organ to store energy and adjust metabolism, it’s metabolism and energy balance are closely related with the body life activities. Therefore, based on the above research foundation and theory, we conceive hepatic energy metabolism and its change has significant correlation with the AFLD, but without enough literature support. Our team preliminary experiment found Gehua Jiejue Dizhi Decoction could significantly ameliorates the formation of liver steatosis, which was better than that of resveratrol. This project plans to probe the changes of hepatic energy metabolism and how SIRT1-AMPK signalling system impact on energy metabolism in vitro and in vivo.Further clarify the molecular mechanism to AFLD occur, at the same time, to provide scientific laboratory basis for the unique advantage of traditional Chinese medicine in the treatment of AFLD.