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目的:从粪便代谢组学层面探讨二至丸抗衰老效应及其潜在作用机制。方法:通过腹腔注射D-半乳糖构建大鼠衰老模型，将动物分为正常对照组、模型对照组及二至丸1、2、4 g/kg组，连续7周灌胃干预后，采用Morris水迷宫评估认知能力；采集血清和粪便样本，利用试剂盒检测大鼠血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、超氧化物歧化酶(SOD)活力和丙二醛(MDA)含量；采用超高效液相色谱-四级杆飞行时间质谱联用技术(UPLC/Q-TOF-MS)分析粪便中差异代谢产物及相关代谢通路。结果:与正常对照组比较，模型对照组逃避潜伏期显著延长，平台穿越次数减少，总游泳距离增加，血清ALT、AST活力和MDA含量显著升高，SOD活力明显降低(P<0.05或P<0.01);与模型对照组比较，二至丸各剂量组大鼠逃避潜伏期显著缩短，平台穿越次数增加，总游泳距离减少，血清ALT、AST活力和MDA含量降低，SOD活力升高(P<0.05或P<0.01)。粪便代谢组学分析显示，二至丸干预可逆转45种差异代谢物的异常表达，表现为胆汁酸、花生四烯酸(AA)及其氧化产物、饱和脂肪酸、甘油二酯(DGs)、鞘磷脂(SMs)和溶血磷脂酰胆碱(LysoPCs)水平下调，油酸(OA)等不饱和脂肪酸水平上调，其抗衰老作用可能与花生四烯酸代谢、甘油磷脂代谢及戊糖-葡萄糖醛酸相互转化的调控密切相关。结论:二至丸可有效改善衰老大鼠的学习记忆能力，其延缓衰老机制可能是通过调控花生四烯酸和甘油磷脂代谢通路实现。
Abstract：Objective:To investigate the anti-aging effects and underlying mechanisms of Erzhi Wan(二至丸) through fecal metabolomic analysis. Methods:An aging rat model was established via intraperitoneal injection of D-galactose. Rats were randomized into a normal control group, a model control group, and Erzhi Wan groups of 4 g/kg, 2 g/kg, and 1 g/kg. After seven weeks of intervention by gavage, cognitive function was evaluated using the Morris water maze. Serum and fecal samples were collected to measure alanine aminotransferase(ALT),aspartate aminotransferase(AST),superoxide dismutase(SOD),and malondialdehyde(MDA) levels via assay kits. Fecal differential metabolites and metabolic pathways were analyzed by ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry(UPLC/Q-TOF-MS). Results:Compared with the normal control group, the model control group showed a significant prolongation in escape latency, a decrease in the number of platform crossings, and an increase in total swimming distance. The level of ALT,AST,and MDA in serum was significantly increased, and the SOD level was significantly reduced(P<0.05 or P<0.01). Compared with the model control group, the Erzhi Wan groups of all doses showed significantly shortened escape latency, increased number of platform crossings, reduced total swimming distance, and decreased level of ALT,AST,and MDA in serum, and increased SOD activity(P<0.05 or P<0.01). Fecal metabolomics showed that 45 differential metabolites were regulated by Erzhi Wan. The level of bile acids, arachidonic acid(AA),oxidized lipids, saturated fatty acids, diacylglycerols(DGs),sphingomyelins(SMs),and lysophosphatidylcholines(LysoPCs) was downregulated, whereas unsaturated fatty acids(OA) were upregulated. The anti-aging effects might be closely related to the interconversion of arachidonic acid metabolism, glycerophospholipid metabolism, and pentose-glucuronic acid. Conclusion:Erzhi Wan effectively improves learning and memory in aging rats, and its anti-aging mechanism may be related to regulating arachidonic acid and glycerophospholipid metabolic pathways.
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基本信息:
DOI：10.13412/j.cnki.zyyl.2026.08.002
中图分类号:R285.5
引用信息:
[1]肖春华,肖昶,朱心榆,等.二至丸通过调节衰老大鼠粪便特征性代谢物延缓衰老[J].中药药理与临床,2026,42(08):2-11.DOI:10.13412/j.cnki.zyyl.2026.08.002.
基金信息:
广东省医学科研基金(编号：A2023420); 广东省医院协会医院药学科研专项基金(编号：YXKY202201); 广州市中医药和中西医结合科技项目(编号：20222A011017); 广州市教育局高校科研项目(编号：2024312065)
2026-08-15
2026-08-15