目的 对经典名方保元汤进行相态拆分，研究不同相态对大鼠运动性疲劳的缓解作用，筛选其有效相态。方法 采用梯度离心-透析法将保元汤拆分为纳米相态（BD nano phase，BD-N）、沉淀相态（BD precipitation phase，BD-P）及真溶液相态（BD solution phase，BD-S），对其外观进行物理学表征，并进行含量测定。建立大鼠游泳疲劳模型，设置对照组、模型组、阳性对照（大株红景天胶囊）组、保元汤组、BD-N组和BD-P组，通过测定行为学指标、脏器指数、血清生化指标及肝组织、肌肉组织病理学变化筛选活性相态。基于肠道微生物组学、代谢组学、转录组学联合分析探讨保元汤及有效相态缓解大鼠运动性疲劳的潜在作用机制，并随机选取其中4个差异表达基因（Gck、Ackr3、Pde4b、Ppp1r3b）进行qRT-PCR验证。结果 BD-N粒子形态呈圆球形且丁达尔效应明显，粒径排序为BD-P＞保元汤＞BD-N；各相态的多分散指数（polydispersity index，PDI）排序为保元汤＞BD-N＞BD-P；各相态ζ电位绝对值排序为BD-P＞BD-N＞保元汤。人参皂苷Rb₁、毛蕊异黄酮-7-O-葡萄糖苷、甘草苷、甘草酸铵、肉桂酸、桂皮醛及6-姜酚均主要分布于BD-N中，综合药效排序为保元汤≈阳性对照药＞BD-N＞BD-P。BD-N调节肠道菌群丰度并增加乳杆菌属水平及其对与疲劳相关的45个差异代谢物的调控能力与保元汤相近；qRT-PCR结果显示，BD-N与保元汤对4个基因的调控趋势与转录组测序结果一致。结论 从物理-化学-药效角度筛选保元汤缓解疲劳作用的有效相态，BD-N为保元汤缓解疲劳的有效相态。

Objective To split the classic prescription Baoyuan Decoction (保元汤) into different phases, study the relieving effects of different phases on exercise fatigue in rats, and screen for their effective phases. Methods The gradient centrifugation dialysis method was used to separate Baoyuan Decoction into the nano phase (BD nano phase, BD-N), precipitation phase (BD-P) and solution phase (BD-S). The appearance was physically characterized and contents of main ingredients was determined. A rat swimming fatigue model was established, control group, model group, positive control (Dazhu Hongjingtian Capsule) group, Baoyuan Decoction group, BD-N group and BD-P group were set up, active phases was screened by measuring behavioral indicators, organ indices, serum biochemical indicators, and pathological changes in liver and muscle tissues. Based on combined analysis of gut microbiome, metabolomics and transcriptomics, the potential mechanism of Baoyuan Decoction and its effective phase in alleviating exercise fatigue in rats was explored. Four differentially expressed genes (Gck, Ackr3, Pde4b, Ppp1r3b) were randomly selected for qRT-PCR validation. Results The particle morphology of BD-N was spherical and Tyndall effect was significant. The particle size was in the order of BD-P > Baoyuan Decoction > BD-N. The polydispersity index (PDI) of each phase was in the order of Baoyuan Decoction > BD-N > BD-P. The absolute value of zeta potential for each phase was BD-P > BD-N > Baoyuan Decoction. Ginsenoside Rb₁, calycosin-7- O-β-D-glucoside, liquiritin, ammonium glycyrrhizinate, cinnamic acid, cinnamaldehyde and 6-gingerol were mainly distributed in BD-N. The comprehensive efficacy ranking was Baoyuan Decoction ≈ positive control drug > BD-N > BD-P. The ability of BD-N in regulating the abundance of gut microbiota, increasing the level of Lactobacillus genus and regulating 45 differential metabolites related to fatigue was similar to Baoyuan Decoction. The qRT-PCR results showed that the regulatory trends of BD-N and Baoyuan Decoction on four genes were consistent with the transcriptome sequencing results. Conclusion From the perspective of physics, chemistry and pharmacological effects, the effective phase of Baoyuan Decoction in relieving fatigue is screened, and BD-N is the effective phase of Baoyuan Decoction in relieving fatigue.

R285.5

吉林省发改委项目（2022C41-7）；吉林省科技发展计划项目（YDZJ202402034CXJD）