目的 采用正交设计结合疾病模型优化金水缓纤方组分配比、评价组分配伍的疗效，获得金水缓纤组分方。方法 10种中药组分作为金水缓纤方候选活性组分，分为不同功效组包括补气组（人参皂苷Re和人参皂苷Rb₁）、补肾组（淫羊藿苷和鲁斯可皂苷元）、活血组（芍药苷和丹皮酚）、化痰组（3， 29-二苯甲酰基栝楼仁三醇、川陈皮素和贝母素甲）、补肺组（异甘草素），以及采用组合法设置补气、补肾和活血组的不同浓度配比组，采用正交设计设置化痰组不同浓度组；基于肺泡上皮细胞评价其活性，肺纤维化大鼠模型评价其疗效，依次优化组内、组间配伍配比。结果 基于正交设计与细胞模型活性评价获得组内配伍：补气组（人参皂苷Re）、补肾组（淫羊藿苷）、化痰组（川陈皮素-贝母素甲2∶12.5）、活血组（芍药苷）、补肺组（异甘草素）；组间配伍：补肾组（淫羊藿苷）-化痰组（川陈皮素-贝母素甲2∶12.5）-活血组（芍药苷）-补气组（人参皂苷Re）-补肺组（异甘草素）为100∶（2∶12.5）∶6.25∶80∶8。金水缓纤组分I可显著改善大鼠肺纤维化症状，并进一步优化了金水缓纤组分I的配伍配比，获得了组分明确、疗效明显的金水缓纤组分II，即为淫羊藿苷-川陈皮素-贝母素甲-芍药苷-异甘草素为100∶2∶6.25∶6.25∶8。结论 组分配伍研究可有效揭示中药复方疗效物质基础，获得组分明确、疗效明显的金水缓纤组分方。

Objective To optimize the distribution ratio of Jinshui Huanxian formula (金水缓纤方, JHF) and evaluate the efficacy of component compatibility (ECC) by orthogonal design combined with disease model, in order to obtain the ECC. Methods Ten active components of JHF were identified and divided into tonifying qi (ginsenoside Re, ginsenoside Rb1), tonifying kidney (icariin, ruscogenin), activating blood (paeoniflorin, paeonol), resolving phlegm (3,29-dibenzoyl rarounitriol, nobiletin and verticine), and tonifying lung (isoliquiritigenin) groups. The different concentration ratio groups of tonifying qi, tonifying kidney and activating blood groups were set by the combination method, and the different concentration groups of the phlegm-reducing group were set by the orthogonal design. Its activities were evaluated based on alveolar epithelial cells, and its efficacy was evaluated based on pulmonary fibrosis (PF) rat model. Intra-group and inter-group compatibility ratio were optimized respectively. Results The compatibility in group was obtained based on orthogonal design combined with cell model: tonifying qi (ginsenoside Re), tonifying kidney (icariin), resolving phlegm (nobiletin: verticine = 2: 12.5), activating blood (paeoniflorin), tonifying lung (isoliquiritigenin); The compatibility among groups: tonifying kidney (icariin): resolving phlegm (nobiletin: verticine = 2: 12.5): activating blood (paeoniflorin): tonifying qi (ginsenoside Re): tonifying lung (isoliquiritigenin) = 100:(2:12.5):6.25:80:8. Then, ECC of JHF I could significantly improve the symptom of PF rats. The active ingredients of effective-component compatibility of ECC-JHF I were optimized based on their therapeutic effect on rat and ECC-JHF II (icariin: nobiletin: verticine: paeoniflorin: isoliquiritigenin = 100:2:6.25:6.25:8) was obtained. Conclusion The study of component compatibility can effectively reveal the material basis of the efficacy of traditional Chinese medicine compound, and the component prescription of JHF with clear components and obvious effect was obtained.

R285

国家自然科学基金面上项目（81673942）；国家自然科学基金面上项目（81973822）