摘要
目的 基于尿液代谢组学及肠道菌群探讨桂仙合剂通过粪菌移植干预绝经综合征潮热的作用机制。方法 将48只雌性SD大鼠随机分为健康组、潮热组、桂仙合剂组、克龄蒙组、健康移植组、潮热移植组、桂仙合剂移植组、克龄蒙移植组,每组6只。健康组、健康移植组、潮热移植组大鼠进行假手术造模,其余组大鼠采用去卵巢手术建立绝经综合征潮热模型。手术10 d后证实造模成功后,健康组和潮热组给予生理盐水灌胃;桂仙合剂组给予桂仙合剂药液33.3 g/kg灌胃;克龄蒙组前3 d予0.4 mg/kg戊酸雌二醇溶液灌胃,后2 d予0.6 mg/kg戊酸雌二醇合醋酸环丙孕酮溶液灌胃。移植各组手术后第10~14天给予抗生素鸡尾酒疗法处理构建肠道相对无菌状态,然后健康移植组给予正常人的粪菌液灌胃,潮热移植组给予潮热患者的粪菌液灌胃,桂仙合剂移植组给予经桂仙合剂治疗的绝经综合征潮热患者的粪菌液灌胃,克龄蒙移植组给予经克龄蒙治疗的绝经综合征潮热患者的粪菌液灌胃。检测各组大鼠尿液代谢物谱并鉴定差异代谢物,进行代谢通路富集分析;取粪便样本进行16S rRNA基因测序,然后进行生物信息分析。结果 桂仙合剂通过干预肠道菌群主要影响了17个生物标志物,这17个生物标志物与膦酸盐和次膦酸盐代谢途径、卟啉代谢、甘氨酸丝氨酸和苏氨酸代谢、嘌呤代谢、类固醇激素生物合成5条代谢通路有关。对这些代谢通路具有重要影响的差异代谢物分别是氨乙基膦酸、5-氨基乙酰丙酸、2-吡咯烷基甘氨酸、黄嘌呤、睾酮。差异菌群为巴士梭菌、多尔菌、放线菌、考拉杆菌,其中巴士梭菌、考拉杆菌均与黄嘌呤呈正相关,与2-吡咯烷基甘氨酸呈负相关。结论 桂仙合剂粪菌移植可能通过调节“肠菌-代谢”轴以发挥治疗绝经综合征潮热的作用。
Objective It is to explore the mechanism of Guizhi and Erxian decoction(GED)in the treatment of menopausal syndrome-vasomotor symptoms(MPS-VMS)through fecal microbiota transplantation based on urine metabolomics and gut microbiota.Methods Forty-eight female SD rats were randomly divided into the following groups:healthy group,VMS group,GED group,Climen group,healthy transplantion group,VMS transplantion group,GED transplantion group,and Climen transplantion group,with 6 rats in each group.The rats in the healthy group,healthy transplantion group,and VMS transplantion group were modeled with sham surgery,while the rats in the remaining groups underwent ovariectomy to establish models of MPS-VMS.After successful modeling was confirmed in 10 days after surgery,the healthy group and VMS group was given physiological saline via gavage;the GED group was given GED compound solution 33.3 g/kg by gavage;the Climen group was given estradiol valerate solution 0.4 mg/kg by gavage for the first 3 days,followed by estradiol valerate combined with cyproterone acetate solution 0.6 mg/kg by gavage for the subsequent 2 days.All the transplantion groups were treated with antibiotic cocktail therapy from 10th to14th day after surgery to achieve relative intestinal sterility.Subsequently,the healthy transplantion group was given fecal microbiota solution from healthy individuals by gavage,the VMS transplantion group was given fecal microbiota solution from VMS patients by gavage,the GED transplantion group was given fecal microbiota solution from MPS-VMS patients treated with GED by gavage,while the Climen transplantion group was given fecal microbiota solution from MPS-VMS patients treated with Climen by gavage.The urinary metabolite profiles of rats in each group were detected,and differential metabolites were identified,and metabolic pathway enrichment analysis was performed;fecal samples was collected for 16S rRNA gene sequencing,followed by bioinformatics analysis.Results GED primarily influenced 17 biomarkers by regulating gut microbiota.These biomarkers were associated with 5 metabolic pathways:phosphonate and phosphinate metabolism,porphyrin metabolism,glycine-serine-threonine metabolism,purine metabolism,and steroid hormone biosynthesis.The differential metabolites significantly influence these pathways included ciliatine,5-aminolevulinic acid,2-pyrrolidine-glycine,xanthine and testosterone.The differential microbial genera were Clostridium baratii,Dorea,Actinomyces,and Phascolarctobacterium,in which Clostridium baratii and Phascolarctobacterium were positively correlated with xanthine and negatively correlated with 2-pyrrolidine-glycine.Conclusion GED fecal microbiota transplantation may exert therapeutic effects on MPS-VSMS by regulating the“gut microbiota-metabolism”axis.
作者
赵婧冰
郭永
黄磊
陈思阳
宗云
周英
ZHAO Jingbing;GUO Yong;HUANG Lei;CHEN Siyang;ZONG Yun;ZHOU Ying(The First Clinical Medical College of Guangzhou University of Chinese Medicine,Guangzhou 510405,Guangdong,China;The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine,Guangzhou 510405,Guangdong,China;Guangdong Clinical Research Institute of Traditional Chinese Medicine,Guangzhou 510405,Guangdong,China)
出处
《现代中西医结合杂志》
2025年第22期3102-3109,共8页
Modern Journal of Integrated Traditional Chinese and Western Medicine
基金
广东省基础与应用基础研究基金企业联合基金项目(2023A1515220027)。
关键词
桂仙合剂
绝经综合征潮热
粪菌移植
尿液代谢组学
Guizhi and Erxian decoction
menopausal syndrome with vasomotor symptoms
fecal microbiota transplantation
urine metabolomics
