基于miR-141/AMPK/SIRT1/UCP2信号通路研究狗肝菜多糖（DCP）对非酒精性脂肪肝（NAFLD）的作用机制

AMPK可调节SIRT1的活性促进糖脂代谢，SIRT1可与UCP2启动子结合抑制解偶联反应改善胰岛素水平，而miR-141可抑制AMPK和SIRT1，上调UCP2的表达加重NAFLD。课题组证实DCP对含NAFLD在内的肝损伤具有显著防治作用，在NAFLD中发现，miR-141和UCP2显著表达，而SIRT1和p-AMPK表达下降，DCP可调控以上指标改善NAFLD，故推测DCP缓解NAFLD与调控miR-141/AMPK/SIRT1/UCP2通路有关。为此，本研究通过体内外实验，应用siRNA、慢病毒转染、Western Blot、Real-time PCR、荧光素酶报告基因及miR-141-/-等基因敲除小鼠等方法,明确miR-141/AMPK/SIRT1/UCP2通路是否为防治NAFLD的新靶标，同时揭示DCP是否通过介导该通路干预NAFLD，为防治NAFLD提供新靶标和潜在药物。

AMPK regulates SIRT1 activity and promotes glucose and lipid metabolism. SIRT1 can bind to UCP2 promoter to inhibit uncoupling reaction and improve insulin level, while miR-141 can inhibit expression of AMPK and SIRT1 and up-regulate UCP2 expression to aggravate NAFLD.The research group confirmed that DCP has a significant protective effect on liver injury including NAFLD.In NAFLD model, we found that miR-141 and UCP2 were significantly expressed, while SIRT1 and AMPK were decreased, and DCP could regulate the above indicators to anti-NAFLD in rats with nonalcoholic fatty liver disease (NAFLD).Therefore, we speculated that DCPintervene NAFLD involvingmiR-141/AMPK/SIRT1/UCP2 pathway.For this purpose, the current study apply siRNA, lentiviral vector, Western Blot, Real-time PCR, luciferase reporter gene assay, miR-141-/-knocked out mice et al to demonstrate whether miR-141/AMPK/SIRT1/UCP2 pathway are new targets for prevention and treatment of NAFLD,and meanwhile to reveal whether DCP counteracts NAFLD via miR-141/AMPK/SIRT1/UCP2 pathway and provide new targets and potential drugs for prevention and treatment of NAFLD.