苦参甘草组方基于“肝脾同治”理论防治非酒精性脂肪性肝炎的作用及其机理研究

Nonalcoholic steatohepatitis (NASH) is a common and frequently occurring disease, which can eventually lead to liver cirrhosis and hepatocellular carcinoma and is currently lacking in effective drugs. The intestinal mucosal barrier damage and intestinal endotoxin into blood which caused by bile acid metabolism abnormal is very important in the pathogenesis of NASH, In addition to insulin resistance. Traditional Chinese medicine believes that the irregular flow of the liver qi causes Flexure Syndrome，Liver disease and spleen transmission、disfunction of the spleen in transport，hisao sputum and accumulating in the liver and causing disease。In previous studies, We are guided by the theory of "liver and spleen phase, liver and spleen with the same treatment"，found that pair of Sophora flavescens - Glycyrrhiza can effectively prevent NASH, the effect is closely related to reduce the content of bacterial endotoxin in bile and the content of bacterial endotoxin in the blood of the portal vein, but the molecular mechanism is unknown. This research would used In vivo and in vitro model, siRNA interference technique, molecular pharmacology and histopathology will used in this research to investigated that Sophora flavescens by activating the orphan nuclear receptor FXR in liver regulates bile acid metabolism; Glycyrrhiza by regulating the zonula occludes protein in intestinal mucosal cells, repair of intestinal mucosal barrier, inhibiting the activation of the TLR4 signaling pathway, which plays a role in prevention and treatment of NASH.It provides an experimental basis for the clinical application of pair of Sophora flavescens - Glycyrrhiza in the prevention and treatment of NASH, and provides a new idea for the study of the prevention and treatment of liver metabolic diseases by "treating with liver and spleen together".

非酒精性脂肪性肝炎（NASH）是一种常见病和多发病，最终可导致肝硬化及肝细胞肝癌，目前缺乏有效治疗药物。近年研究表明，除胰岛素抵抗外，胆汁酸代谢异常，及其导致的肠粘膜屏障损伤、肠道内毒素大量入血，是NASH的重要发病机制之一。中医认为，肝失疏泄以致气机阻滞，肝病传脾、脾失运化，日久生痰阻于肝而成本证。在以往的研究中，我们以“肝脾相维、肝脾同治”理论为指导，发现苦参甘草组方可有效防治NASH，该作用与改善NASH模型小鼠胆汁酸的代谢异常，减少内毒素的吸收密切相关，但具体分子机理不详。本课题拟采用在体和离体模型、siRNA干扰技术、分子药理学和组织病理学等方法，研究苦参通过激活肝脏孤核受体FXR，调节胆汁酸代谢；甘草通过上调肠上皮细胞紧密连接蛋白表达，修复肠粘膜屏障，协同防治NASH的作用机制；为苦参甘草组方防治NASH的临床应用提供实验依据，为“肝脾同治”防治肝脏代谢性疾病的研究提供新思路。

非酒精性脂肪性肝炎（NASH）是一种常见病和多发病，最终可导致肝硬化及肝细胞肝癌，目前缺乏有效治疗药物。近年研究表明，除胰岛素抵抗外，胆汁酸代谢异常，及其导致的肠粘膜屏障损伤、肠道内毒素大量入血，是NASH的重要发病机制之一。中医认为，肝失疏泄以致气机阻滞，肝病传脾、脾失运化，日久生痰阻于肝而成本证。在以往的研究中，我们以“肝脾相维、肝脾同治”理论为指导，发现苦参甘草组方可有效防治NASH，该作用与改善NASH模型小鼠胆汁酸的代谢异常，减少内毒素的吸收密切相关，但具体分子机理不详。本课题采用在体和离体模型、siRNA干扰技术、分子药理学和组织病理学等方法，研究苦参通过激活肝脏孤核受体FXR，调节胆汁酸代谢；甘草通过上调肠上皮细胞紧密连接蛋白表达，修复肠粘膜屏障，协同防治NASH的作用机制；为苦参甘草组方防治NASH的临床应用提供实验依据，为“肝脾同治”防治肝脏代谢性疾病的研究提供新思路。