中性粒细胞Proteinase 3靶向的溪黄草干预NASH肝纤维化药效物质基础和作用机制研究

非酒精性脂肪肝炎（NASH）可发展为肝纤维化、肝硬化及肝癌，尚无有效临床治疗药物。课题组在前期研究中发现了干预NASH肝纤维化的潜在创新靶点Proteinase 3 (PR3)。中医药治疗慢性肝病优势明显，溪黄草为岭南特色中药，在临床多用于肝病治疗。课题组发现溪黄草能够改善小鼠NASH肝纤维化，抑制LPS诱导的骨髓细胞中PR3表达，提示其护肝功效可能与抑制PR3发挥抗NASH肝纤维化的药效相关，但其物质基础及作用机制有待深入研究。本项目拟基于NASH肝纤维化动物模型，筛选溪黄草抗NASH肝纤维化的有效部位及活性成分；以PR3为靶标，利用分子对接技术结合体内外活性评价确定溪黄草抗NASH肝纤维化的药效物质，深入解析溪黄草调控PR3进而阻断NASH肝纤维化的作用机制。本研究将揭示溪黄草抑制PR3并干预NASH的药效物质基础，阐明其护肝传统功效的作用机制，为其临床应用提供科学依据。

Non-alcoholic steatohepatitis (NASH) can exacerbate the risk for the progression to liver fibrosis, cirrhosis, and hepatocellular carcinoma. Currently, NASH fibrosis-specific therapies are approved clinically. .Explicit advantages are well-defined that Traditional Chinese medicine in curing chronic liver diseases. As a characteristic traditional Chinese medicine in Lingnan district, monomer and formula of Xihuangcao (Rabdosia serra (Maxim.) Hara) are widely used to ameliorate liver diseases in clinical. from ancient Preliminary studies lay the foundation that the extract of traditional Chinese Medicine Xihuangcao could improve the NASH fibrosis in mouse model, counter the Proteinase 3 (PR3) expression in LPS-induced bone marrow cells, together with suggesting Xihuangcao-mediates inhibition of PR3 expression might be the possible way to combat NASH fibrosis, while the underlying mechanism is still remains intricate and warrants investigation. In this project, on the strength of PR3 and NASH fibrosis animal model, we intend to unveil the effective component and active compound of Xihuangcao which countering NASH fibrosis. Tarting PR3, molecular docking technology combined with in vivo and in vitro activity evaluation will be applied to determine the inciting compound of Xihuangcao against NASH fibrosis, which enable us to elucidate the molecular mechanism of Xiahuangcao alleviates NASH fibrosis by mediating PR3 sabotage. This study will provide solid experimental evidence for the pharmacological material basis of Xihuangcao to inhibit PR3 and interfere with NASH fibrosis, illuminating the mechanism of its liver-protecting effect, as well as scientific foundation for clinical practice.