基于代谢组学和肠道菌群探讨知柏地黄改良食疗方对幼龄性早熟大鼠的影响OA
Effects of Zhibai Dihuang Modified Dietary Formula(知柏地黄改良食疗方)on precocious puberty in juvenile rats:insights from metabolomics and gut microbiota
目的 探析知柏地黄改良食疗方对性早熟模型大鼠的干预作用及其潜在机制.方法 采用达那唑诱导SD大鼠建立性早熟模型.设置空白组、模型组及食疗方组(n=8).通过ELISA法检测血清促黄体生成素(LH)、促卵泡生成素(FSH)和雌二醇(E2)等性激素水平;计算子宫/卵巢脏器指数;通过石蜡切片HE染色观察子宫和卵巢的病理变化;联合16S rRNA测序与UHPLC-QTOF-MS代谢组学技术,分析肠道菌群结构演变及血清代谢物变化.结果 模型组大鼠血清LH、FSH、E2水平显著升高(P<0.01),子宫和卵巢脏器指数显著增大(P<0.01),而食疗方干预后上述指标均显著降低(P<0.01).肠道菌群分析显示,食疗方恢复α多样性(Shannon、ACE指数升高,P<0.01),抑制促炎菌属(如Escherichia-Shigella),促进益生菌(如Bifidobacterium、Akkermansia)增殖,并通过β多样性分析证实其菌群组成与空白组趋近.代谢组学研究表明,食疗方显著调控GnRH信号通路(P=0.0400)、花生四烯酸代谢相关通路,缓解性激素诱导的氧化应激,恢复短链脂肪酸(如丁酸)和谷胱甘肽代谢平衡.Procrustes分析进一步揭示肠道菌群与代谢物变化具有显著协同性(P<0.01).结论 知柏地黄改良食疗方可有效缓解性早熟症状指标,其机制可能与重塑肠道菌群结构、抑制炎症反应及多靶点调节代谢通路相关,为知柏地黄改良食疗方干预性早熟提供了理论依据,为其食疗产品开发奠定了功用与机制基础.
Objective To investigate the therapeutic effects and underlying mechanisms of a Zhibai Dihuang Modified Dietary Formula(知柏地黄改良食疗方,ZDMDF)on precocious puberty in rats.Methods A precocious puberty model was established in Sprague-Dawley(SD)rats(n=8 per group)using danazol induction,with three experimental groups:control,model,and ZDMDF intervention.Serum levels of luteinizing hormone(LH),follicle-stimulating hormone(FSH),and estradiol(E2)were measured via ELISA.Uterine and ovarian organ indices were calculated,and histopathological changes were evaluated using paraffin-embedded hematoxylin-eosin(HE)staining.Gut microbiota(GM)composition and serum metabolite profiles were analyzed via 16S rRNA gene sequencing(Illu-mina MiSeq platform)and UHPLC-QTOF-MS-based non-targeted metabolomics,respectively.Results The model group exhibited sig-nificantly elevated serum LH,FSH,and E2 levels(P<0.01),along with increased uterine/ovarian indices(P<0.01),all of which were markedly attenuated by ZDMDF treatment(P<0.01).GM analysis revealed that ZDMDF restored the alpha-diversity(increased Shan-non and ACE indices,P<0.01),suppressed pro-inflammatory genera(e.g.,Escherichia-Shigella),and promoted the proliferation of probiotics(e.g.,Bifidobacterium,Akkermansia),with β-diversity analysis confirming microbiota realignment toward the control group.Metabolomic profiling revealed significant modulation of gonadotropin-releasing hormone(GnRH)signaling(P=0.040),arachi-donic acid metabolism-related pathways,and oxidative stress pathways,accompanied by restored short-chain fatty acids(e.g.,butyr-ate)and glutathione metabolic homeostasis.Procrustes analysis demonstrated strong concordance between GM and metabolomic shifts(P<0.01).Conclusion ZDMDF alleviates precocious puberty by remodeling GM structure,mitigating inflammation,and multi-target regulation of metabolic pathways.These findings provide mechanistic evidence supporting ZDMDF as a dietary intervention for preco-cious puberty and lay a foundation for its clinical translation.
陈星;石强;刘英;何媛;敖梅英;刘潜
江西中医药大学中西医结合一级学科平台,江西 南昌 330006||江西中医药大学中医学院中西医结合儿童健康研究院,儿童药物创新研究中心,江西 南昌 330006||江西省教育厅儿童用中药创新研究重点实验室,江西 南昌 330004江西中医药大学附属医院,江西省中医院,江西 南昌 330004江西中医药大学附属医院,江西省中医院,江西 南昌 330004江西中医药大学附属医院,江西省中医院,江西 南昌 330004江西中医药大学中西医结合一级学科平台,江西 南昌 330006||江西中医药大学中医学院中西医结合儿童健康研究院,儿童药物创新研究中心,江西 南昌 330006||江西中医药大学循证医学研究中心,江西 南昌 330006江西中医药大学中西医结合一级学科平台,江西 南昌 330006||江西中医药大学中医学院中西医结合儿童健康研究院,儿童药物创新研究中心,江西 南昌 330006||江西省教育厅儿童用中药创新研究重点实验室,江西 南昌 330004
医药卫生
性早熟知柏地黄改良食疗方药食同源肠道菌群非靶向代谢组学
Precocious pubertyZhibai Dihuang Modified Dietary Formula(知柏地黄改良食疗方)Medicinal and food homol-ogyGut microbiotaNon-targeted metabolomics
《时珍国医国药》 2026 (10)
1819-1829,11
江西省科技厅省级科技专项资金项目(20243BCC31008)江西中医药大学科研培育项目(2023ZDPY001)江西中医药大学校级重点领域科技创新团队项目(CXTD22014)江西中医药大学校级教改项目(2022jzyx-2)
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