目的 基于代谢组学揭示经典名方补骨脂丸（盐补骨脂-盐小茴香方，Y-BGZW）通过盐制补骨脂改善肾阳虚大鼠肾功能的化学-生物学机制。方法 将50只SD大鼠随机分为对照组、模型组、生制-补骨脂丸（S-BGZW）组(生补骨脂-盐小茴香方，S-BGZW,8 g·kg^-1)、Y-BGZW(8 g·kg^-1)组及金匮肾气丸组(JKSQW,3.5 g·kg^-1)，除对照组外，采用氢化可的松诱导肾阳虚大鼠模型。通过脏器指数分析，ELISA法检测大鼠血清血肌酐（SCr）、尿素氮（BUN）、白细胞介素-2（IL-2）、白细胞介素-6（IL-6）、促肾上腺皮质激素释放激素（CRH）-促肾上腺皮质激素（ACTH）-环磷酸腺苷（cAMP）[下丘脑-垂体-肾上腺轴（HPA）]水平；结合非靶向代谢组学筛选Y-BGZW与S-BGZW中差异代谢物，并通过通路富集与关联分析阐明效应机制。结果 与模型组比较，Y-BGZW显著逆转肾阳虚大鼠脾脏、胸腺萎缩及肾上腺的代偿性增生（P<0.01、0.001），其效果优于S-BGZW，其中脾脏指数差异显著（P<0.001）;Y-BGZW显著上调血清SCr、IL-2、CRH、ACTH、cAMP水平，显著下调BUN、IL-6水平（P<0.01、0.001）,BUN、CRH、c AMP恢复度显著优于S-BGZW（P<0.05、0.001）；代谢组学筛选出10种盐制特征成分（牛蒡子素、羟苯环嘧等），通过甘氨酸/丝氨酸/苏氨酸代谢通路调节水盐平衡（Na⁺/K⁺/Ca²⁺），协同改善肾功能：牛蒡子素调控电解质转运、羟苯环嘧增强膀胱储尿、菊苣素7-（6-丙二酰葡萄糖苷）抑制肾脏氧化损伤、苯甲酰胺保护肾单位、亚麻酸乙酯经CRH通路抑制炎症提升SCr与BUN至正常水平等。结论 从成分-通路-效应3层面验证“盐制入肾”理论的科学内涵，揭示Y-BGZW通过炮制工艺富集特征成分群，经多靶点协同（水盐代谢-抗氧化-免疫调节）实现“温肾固精”功效。

Objective To reveal the chemical-biological mechanism by which the classical formula Psoralea Pill（Salt-processed Psoraleae Fructus-Salt-processed Foeniculi Fructus formula, Y-BGZW） improves renal function in kidney-yang deficiency polyuria rats through salt-processing Psoraleae Fructus, based on metabolomics. Methods The hydrocortisone was used to induce a rat model of kidney yang deficiency, and the 50 SD rats were divided into the following groups: Control group, model group, crude Psoralea Pill group(S-BGZW, 8 g·kg^-1), Y-BGZW(8 g·kg^-1) and Jinkui Shenqi Wan group(JKSQW, 3.5 g·kg^-1). Organ indices were analyzed, and serum biochemical parameters including serum creatinine（SCr）, blood urea nitrogen（BUN）, IL-2, IL-6, and HPA axis markers（CRH, ACTH, cAMP） were quantified by ELISA. Untargeted metabolomics was employed to identify differential metabolites between YBGZW and S-BGZW, with subsequent pathway enrichment and correlation analyses to elucidate the underlying mechanisms. Results Compared with the model group, Y-BGZW significantly reversed splenic and thymic atrophy and compensatory adrenal hyperplasia in rats with kidney yang deficiency（P ＜0.01, 0.001）, and its effect was superior to S-BGZW, with a significant difference in spleen index（P ＜0.001）; Y-BGZW significantly upregulated serum levels of SCr, IL-2, CRH, ACTH, and c AMP, and significantly downregulated levels of BUN and IL-6（P ＜0.01, 0.001）. The recovery of BUN, CRH, and cAMP was significantly better than that of S-BGZW（P ＜0.05, 0.001）. Metabolomics screening identified ten characteristic components of salt-processed Psoralea corylifolia（e.g., arctigenin, hydroxyphenylcyclamide）, which regulated water-salt balance(Na⁺/K⁺/Ca²⁺) via the glycine/serine/threonine metabolic pathway and synergistically improved renal function:① Arctigenin regulates electrolyte transport.② Hydroxyphenylcyclamide enhances bladder urine storage.③ cichoriin 7-（6-malonylglucoside） inhibits renal oxidative damage.④ Benzamide protects nephrons, ethyl linolenate inhibits inflammation via the CRH pathway, and SCr/BUN levels are restored to normal. Conclusion This study validates the scientific foundation of the “salt-processing guiding to the kidney（Yanzhi Rushen）” theory from three dimensions—components, pathways, and effects, revealing that Y-BGZW enriches characteristic component clusters through its processing method. These components synergistically act on multiple targets（e.g., water-salt metabolism, antioxidant activity, and immune regulation） to achieve the traditional efficacy of “warming the kidney and consolidating essence（Wenshen Gujing）”.

R285

甘肃省高等学校创新基金项目(2023B-263); 甘肃医学院2023年院(系)主任负责制项目(GY-2023FZZ04)