目的 研究山蜡梅叶颗粒活性成分对慢性咽炎模型大鼠的药效作用并建立药动学-药效学（pharmacokinetic-pharmacodynamic，PK-PD）结合模型，构建山蜡梅叶颗粒活性成分的动态变化与其药效消长的对应关系。方法 利用氨水溶液诱导建立慢性咽炎大鼠模型。ig给予山蜡梅叶颗粒，并从行为学特征、咽部组织病理、血清炎症因子含量来考察其治疗效果。以山蜡梅叶颗粒中具有抗炎活性的6个入血成分（原儿茶酸、芦丁、山柰酚-3-O-芸香糖苷、木犀草素、紫云英苷、异嗪皮啶）为药动学考察指标，以血清中炎症因子肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）、白细胞介素-1β（interleukin-1β，IL-1β）和IL-6水平作为药效学指标，利用Phoenix WinNonlin软件构建PK-PD模型。结果 给予山蜡梅叶颗粒后，大鼠血清中TNF-α、IL-1β和IL-6水平较模型组有所降低，咽部组织病理形态改善。建立的PK-PD模型提示山蜡梅叶颗粒抗慢性咽炎药效的发挥与其各成分和整合成分的血药浓度存在滞后现象。结论 山蜡梅叶颗粒具有明显的抗慢性咽炎作用，可能与下调炎症因子水平有关。山蜡梅叶颗粒各成分及整合成分的血药浓度与药物效应值存在滞后现象，这可能是因为山蜡梅叶颗粒中的有效成分进入机体内并不会马上作用于相应的靶点，而是通过间接机制产生药理作用、受体存在耐受现象及受体被激活的时间存在延迟等。

Objective To investigate the effects of active ingredients of Chimonanthus nitens Leaf Granules (山蜡梅叶颗粒, CNLG) on rats with chronic pharyngitis and establish a combined pharmacokinetic-pharmacodynamic (PK-PD) model to construct the dynamic changes of the active ingredients of CNLG and their pharmacodynamic effects. Methods A rat model of chronic pharyngitis was established by using ammonia solution induction, and rats were ig CNLG, therapeutic effect of CNLG was evaluated based on behavioral characteristics, pharyngeal tissue pathology and inflammatory factor levels in serum. PK-PD model was constructed by using Phoenix WinNonlin software, using the six blood components (protocatechuic acid, rutin, kaempferol-3-O-rutinoside, luteolin, astragalin, isofraxidin) with anti-inflammatory activity in CNLG as PK indicators and levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) and IL-6 in serum as PD indicators. Results The levels of TNF-α, IL-1β and IL-6 levels in serum were reduced and pathological morphology of pharyngeal tissue was improved after the administration of CNLG compared with model group. The established PK-PD model suggested that there was a lag between the anti-chronic pharyngitis efficacy of CNLG and the blood concentration of its components and integrated components. Conclusion CNLG has a significant anti-chronic pharyngitis effect, which may be related to the down-regulation of TNF-α, IL-1β and IL-6 levels. There was a lag between the blood concentration and drug effect values of each component and integrated component of CNLG. This may be due to the fact that the active ingredient in CNLG does not act on the target immediately, but through an indirect mechanism of pharmacological action, the receptor tolerance phenomenon and the delay in the activation of the receptor.

R285.61

国家重点研发计划中医药现代化研究重点专项（2018ZX09721002）；江西省人事厅博士后科研项目（252591）；江西省研究生创新专项资金项目（YC2022-s849）；江西省三区人才专项项目；江西省教育厅科学技术研究项目（GJJ211239）；江西中医药大学中药学一流学科科研项目（JXSYLXK-ZHYAO049）；江西中医药大学校级科技创新团队发展计划项目（CXTD-22004）