基于肠道菌Akkermansia muciniphila/SCFAs/GPR43通路研究金丝桃苷改善非酒精性脂肪肝的作用及其机制

非酒精性脂肪肝（NAFLD）作为一种临床常见的代谢综合征，目前尚无理想治疗药物。肠道菌群及其代谢产物短链脂肪酸（SCFAs）是NAFLD发生发展的重要影响因素，其通过影响肠黏膜屏障功能而影响肝脏炎症及脂质积累的发生。申请人前期研究表明护肝清脂片防治NAFLD与调控肠道菌群结构密切相关，而金丝桃苷作为其主要成分之一，预实验结果显示其可显著改善高脂饮食小鼠肝脏脂滴沉积及各项生化指标，通过提高肠道菌Akkermansia muciniphila丰度改善肠道SCFAs失调，明显恢复肠黏膜屏障功能，改善NAFLD。由此假说：金丝桃苷可能通过调控Akkermansia muciniphila/SCFAs/GPR43通路改善肠屏障功能，从而延缓NAFLD的进程。本项目拟采用伪无菌小鼠模型、16S rRNA测序等进行体内外实验深入研究，阐明金丝桃苷对NAFLD的作用机制，为其作为临床用药开发提供依据。

Non-alcoholic fatty liver disease (NAFLD) is a metabolic-related liver disease, and no ideal drugs to heal it in currently. Recent studies showed that gut microbiota and its metabolites, short-chain fatty acids (SCFAs), are important factors in the development of NAFLD, which regulating the inflammation and lipid accumulation in liver by affecting the intestinal barrier function. Our previous results showed that the therapeutic effects of Huganqingzhi tablet in NAFLD are closely related to gut microbiota regulation. As one of the main ingredients of Huganqingzhi tablet, our results showed that hyperoside significantly alleviated the lipid accumulation of liver as well as improved the liver biochemical indexes of NAFLD mice. Moreover, hyperoside markedly increased the abundance of Akkermansia muciniphila, so that improved the dysregulation of SCFAs in intestine and restored the function of intestinal mucosal barrier. Therefore, we proposed a hypothesis that hyperoside may against intestinal barrier function disruption-induced NAFLD by regulating Akkermansia muciniphila/SCFAs/GPR43 pathway. In this study, we are combining in vitro with in vivo study to clarify the mechanism of hyperoside on NAFLD and by using pseudo-germfree mice model induced by antibiotics and 16S rRNA sequensing et al methods, in order to provide scientific basis for the development of hyperoside as a new drug for the treatment of NAFLD.