目的 基于代谢组学技术，系统探究经典名方保元汤对D-半乳糖诱导亚急性衰老模型大鼠的抗衰老作用及潜在机制，为其抗衰老的临床应用与机制研究提供实验依据。方法 将40只SD雄性大鼠随机分为对照组、模型组、维生素E（阳性药）组和保元汤低、高剂量(1.3、2.6 g·kg^-1)组，除对照组外，其余各组通过ip 500 mg·kg^-1 D-半乳糖构建衰老大鼠模型，各组同步ig给药42 d。实验结束后检测大鼠脏器指数，采用苏木素-伊红（HE）染色观察肾组织病理形态；试剂盒检测血清及肾组织中丙二醛（MDA）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）水平及血清尿素氮（BUN）、肌酐（CRE）含量；蛋白免疫印记法检测肾组织中凋亡相关蛋白BCL2相关X蛋白基因（Bax）、B淋巴细胞瘤-2基因（Bcl-2）、半胱氨酸-天冬氨酸蛋白酶-3（Caspase-3）及其剪切体（cleaved-Caspase-3）的表达；基于UPLC-Q-TOF-MS技术开展血清代谢组学分析，筛选差异代谢物并进行代谢通路富集。结果 与对照组相比，模型组大鼠各脏器指数显著降低（P<0.01、0.001），肾组织出现肾小球萎缩、肾小管上皮细胞坏死等病理损伤，血清及肾组织SOD、GSH-Px水平显著降低、MDA含量显著升高（P<0.001），血清BUN、CRE水平显著上升（P<0.001），肾组织Bax表达及Cleaved-caspase-3/Caspase-3、Bax/Bcl-2值显著升高、Bcl-2表达显著降低（P<0.01、0.001），血清中212种内源性代谢物发生显著异常。与模型组相比，保元汤各剂量可显著改善大鼠脏器萎缩及肾组织病理损伤（P<0.05、0.01、0.001），上调血清及肾组织SOD、GSH-Px活性，下调MDA含量及血清BUN、CRE水平，逆转肾组织凋亡相关蛋白的异常表达；其中保元汤高剂量可显著回调35种衰老相关差异代谢物，富集得到25条代谢通路，核心调控花生四烯酸代谢、视黄醇代谢、丙氨酸-天冬氨酸和谷氨酸代谢通路。结论 保元汤可通过改善衰老大鼠脏器萎缩、修复肾组织病理损伤、缓解机体氧化应激、抑制肾组织细胞凋亡，并调控多条核心代谢通路稳态，多维度、多靶点发挥抗衰老作用，其对肾组织的保护作用是其抗衰老的重要机制之一。

Objective Based on metabolomics technology, this study systematically explored the anti-aging effect and potential mechanism of the classic formula Baoyuan Decoction on D-galactose-induced subacute aging model rats, providing experimental evidence for its clinical application and mechanism research of anti-aging. Methods Forty male SD rats were randomly divided into the control group, model group, vitamin E（positive drug） group, low-dose and high-dose(1.3, 2.6 g·kg^-1) Baoyuan Decoction groups. Except for the control group, the other groups constructed the aging rat model by ip administration of 500 mg kg^-1 D-galactose, and all groups were given ig administration simultaneously for 42 d. After the experiment, the organ indices of rats were detected, and the pathological morphology of renal tissue was observed using hematoxylin-eosin（HE） staining; serum and renal tissue levels of malondialdehyde（MDA）, superoxide dismutase（SOD）, glutathione peroxidase（GSH-Px）, and serum urea nitrogen（BUN）, creatinine（CRE） contents were detected using kits; the expression of apoptosis-related proteins BCL2-related X protein gene（Bax）, B lymphocyte tumor-2 gene（Bcl-2）, cysteine-aspartic acid protease-3（Caspase-3） and its cleaved form（cleaved-Caspase-3） in renal tissue was detected by protein immunoblotting; serum metabolomics analysis was conducted based on UPLC-Q-TOF-MS technology to screen differential metabolites and perform metabolic pathway enrichment. Results Compared with the control group, the organ indices of rats in the model group were significantly decreased（P < 0.01, 0.001）, renal tissue showed glomerular atrophy, renal tubular epithelial cell necrosis and other pathological damages, serum and renal tissue SOD, GSH-Px levels were significantly decreased, MDA content was significantly increased（P < 0.001）, serum BUN, CRE levels were significantly increased（P < 0.001）, bax expression and cleavedCaspase-3/Caspase-3, Bax/Bcl-2 values were significantly increased, Bcl-2 expression was significantly decreased（P < 0.01, 0.001）, and 212 endogenous metabolites in serum showed significant abnormalities. Compared with the model group, the high-dose groups of Baoyuan Decoction could significantly improve the organ atrophy and renal tissue pathological damage of rats（P < 0.05, 0.01, 0.001）, up-regulate the activities of serum and renal tissue SOD, GSH-Px, down-regulate MDA content and serum BUN, CRE levels, reverse the abnormal expression of apoptosis-related proteins in renal tissue; among them, the high-dose group of Baoyuan Decoction could significantly restore 35 aging-related differential metabolites, and 25 metabolic pathways were enriched, with core regulatory pathways of arachidonic acid metabolism, retinol metabolism, alanine-aspartic acid and glutamic acid metabolism. Conclusion Baoyuan Decoction can exert anti-aging effects through improving organ atrophy in aging rats, repairing renal tissue pathological damage, alleviating oxidative stress in the body, inhibiting renal tissue cell apoptosis, and regulating multiple core metabolic pathways homeostasis, and exerting multi-dimensional and multi-target anti-aging effects. Its protective effect on renal tissue is one of the important mechanisms of its anti-aging.

R285.5

江西中医药大学校级科技创新团队发展计划(CXTD22002); 2024年中药科研实践创新训练项目(24KYCX-YB038); 省级“大学生创新创业训练计划”项目(S202510412141)