目的 筛选三七抗瘢痕成纤维细胞（human hypertrophic scar fibroblasts，HSF）增殖作用的有效成分并研究其作用机制。方法 采用索氏提取法将三七药材按照极性依次提取；以MTS法筛选其中具有较好抗HSF增殖作用的提取物，结合流式细胞仪检测其对细胞周期的影响；进一步采用HPLC对其有效成分进行谱效分析，将其中高活性成分进行UPLC-Q/TOF-MS鉴定及验证，通过反向对接技术预测有效成分的抗增殖作用机制。结果 三七醋酸乙酯提取部位有较高的抗HSF细胞增殖活性（P＜0.01），能显著增加G₀/G₁期细胞的比例（P＜0.01），降低增殖指数（proliferation index，PI）（P＜0.01），其中主要活性成分为皂苷类化合物；以人参皂苷Rh₁和人参皂苷Rg₁为例的验证结果显示，这2种成分均能抑制细胞的增殖且呈剂量依赖性。反向对接预测结果显示，皂苷类化合物可能通过MAP2K1、MAPK14、HRAS等靶点作用于抗HSF细胞增殖相关信号通路。结论 三七醋酸乙酯提取物对瘢痕成纤维细胞增殖有抑制作用，主要成分为其中的皂苷类化合物，其作用机制可能与调节MAPK、黏着斑等信号通路有关。

Objective To screen the components with potent antiproliferative effects on human hypertrophic scar fibroblasts (HSF) in Panax notoginseng and to explore their mechanisms. Methods The Soxhlet extraction method was used to obtain the different extracts from P. notoginseng by solvents with different polarities. MTS method was used to screen the ingredients with antiproliferative activity on HSF and flow cytometry was used to detect their influence on cell cycle. Then, spectrum-activity relationship of the active ingredients was analyzed by HPLC. UPLC-Q/TOF-MS was used to identify the ingredients with obvious activity. The antiproliferative mechanism was predicted by reverse docking. Results The ethyl acetate extract of P. notoginseng showed higher antiproliferative activity (P < 0.01), significantly increased the proportion of cells in G₀/G₁ phase (P < 0.01), and reduced the proliferation index (PI) (P < 0.01). The main active components were saponins. The result of confirming experiment showed that ginsenosides Rh₁ and Rg₁ could inhibit the cell proliferation in a dose-dependent manner. Results of reverse docking indicated the antiproliferative effects might be related to the regulation of some target proteins such as MAP2K, MAPK14, and HRAS, as well as the related pathways. Conclusion The ethyl acetate extract of P. notoginseng shows the antiproliferative activity on HSF, and the antiproliferative ingredients are saponins. The underlying mechanisms might be related with the regulation of MAPK and focal adhesion signaling pathways.

国家自然科学基金资助项目（81173638，81102835，81001682）