成纤维细胞活化导致纤维化的发生。线粒体丙酮酸转运和谷氨酰胺分解为细胞增殖分化提供必需的碳源和氮源。由于细胞代谢的可塑性，单一源头抑制可通过代谢重构经其它路径代偿，凸显了联合阻断线粒体丙酮酸转运和谷氨酰胺分解抑制成纤维细胞活化的必要性。课题组前期发现丹参-三七药对可抵抗小鼠肝纤维化，且效果显著优于单独给药，提示药对中存在协同增效成分；发现丹参、三七中活性成分可分别抑制线粒体丙酮酸转运体MPC和谷氨酰胺分解酶GLS。据此，本项目提出假说：丹参-三七药对可通过协同抑制线粒体丙酮酸转运和谷氨酰胺分解遏制肝纤维化的发生。拟采用肝纤维化动物、细胞模型，评价丹参-三七药对抗肝纤维化的作用；采用靶标垂钓和拟合分析，发现抑制MPC和GLS的协同成分组合；应用基因沉默与过表达技术，阐明协同成分组合抑制成纤维细胞增殖的作用机制。研究成果将为肝纤维化的治疗提供新靶点，为抗肝纤维化药物的发现提供新思路。

The activation of fibroblast cells is the critical step in the occurrence and development of hepatic fibrosis. Pyruvate transferring into mitochondria and glutamine decomposition provide carbon and nitrogen sources for cell proliferation. The figurability of metabolism indicates that inhibition of one process in cells may lead to the activation of the other metabolic pathway. According to this principle, it is imperative to inhibit these two processes simultaneously in the process of restraining cell proliferation. Our previous study indicated that Danshen-Sanqi herb pair alleviated hepatic fibrosis induced by carbon tetrachloride in mice, and herb combinations showed better effects than single administration. These results indicated that Danshen-Sanqi herb pair may contain compounds which exert synergistic effects. Meanwhile, our results showed that ginsenoside in Sanqi and tanshinone in Danshen restrain MPC and GLS, which are the key regulatory enzymes of pyruvate transferring into mitochondria and glutamine decomposition process, respectively. Based on the above research, we propose a hypothesis that Danshen-Sanqi herb pair has synergistic inhibitory effects on the treatment of hepatic fibrosis. Concrete research content including following several aspects. Firstly, we will use animal and cell models to evaluate the alleviative effect of Danshen-Sanqi herb pair on hepatic fibrosis; secondly, utilize target fishing and fitting analysis to discover the synergistic action components; thirdly, employ knockout and overexpression technology to illuminate the mechanism of synergistic action components on inhibitory of cell proliferation. This project will provide new targets for the treatment of hepatic fibrosis and further propose new ideas on drug discovery in anti-hepatic fibrosis.