文献类型：期刊文献

中文题名：联合微生物组学和代谢组学研究党参水提物调节衰老小鼠肠道屏障和菌群代谢的作用机制

英文题名：Combining Microbiomics and Metabolomics to Study Mechanism of Dangshen(Codonopsis pilosula)Water Extract in Regulating Intestinal Barrier and Microbial Metabolism in Aging Mice

作者：王晶[1];王振娟[1];康甲超[1];韩乐[1];柳立军[2];吴萍民[3];段永强[4]

第一作者：王晶

机构：[1]甘肃中医药大学公共卫生学院,甘肃兰州730000;[2]兰州大学第一医院,甘肃兰州730000;[3]甘肃中医药大学教学实验实训中心,甘肃兰州730000;[4]宁夏医科大学中医学院,宁夏银川750000

第一机构：甘肃中医药大学公共卫生学院

年份：2025

卷号：43

期号：7

起止页码：29

中文期刊名：中华中医药学刊

外文期刊名：Chinese Archives of Traditional Chinese Medicine

收录：;北大核心:【北大核心2023】；

基金：国家自然科学基金项目(82060829);甘肃省自然科学基金项目(23JRRA1720);甘肃中医药大学研究生创新创业基金项目(2023CX)。

语种：中文

中文关键词：代谢组学;16S rDNA;衰老;肠道菌群;党参

外文关键词：metabolomics;16SrDNA;aging;gut microbiota;Dangshen(Codonopsis pilosula)

摘要：目的揭示党参水提物对衰老模型小鼠肠道屏障和菌群代谢的保护作用。方法选取50只无特定病原体(Specific pathogen free,SPF)级8周龄C57BL/6小鼠随机分为5组,构建D-半乳糖小鼠衰老模型,并用不同剂量党参水提物进行干预。生化分析小鼠血清中超氧化物歧化酶(Superoxide dismutase,SOD)、丙二醛(Malondialdehyde,MDA)、脂质过氧化物(Lipid peroxidation,LPO)的含量;运用苏木素-伊红(Haematoxylin Eosin,HE)染色观察小鼠肠道组织病理学变化;应用免疫组织化学染色观察小鼠肠道组织Occludin和Claudin 1蛋白的表达情况;透射电子显微镜观察小鼠肠道组织细胞超微结构;联合16S rDNA测序和代谢组学分析衰老及党参干预后小鼠肠道菌群和代谢物的变化,再通过生物学信息学进行关联分析。结果与正常对照组相比,衰老小鼠体质量及摄食量降低(P<0.05),党参低、中、高剂量组比衰老组显著增加(P<0.05);与正常对照组相比,衰老模型组血清SOD下降(P<0.05),MDA、LPO水平升高(P<0.05),党参低、中、高剂量组显著逆转了SOD、MDA、LPO的变化水平(P<0.05);衰老模型小鼠的肠道组织结构明显损伤,Occludin和Claudin 1蛋白表达和正常对照组相比显著下降(P<0.05);高剂量党参干预后,肠道组织损伤有明显改善,Occludin和Claudin 1蛋白表达均明显增加(P<0.05),小鼠肠道细胞超微结构趋于正常。小鼠衰老过程中,拟杆菌门(Bacteroidota)比厚壁菌门(Firmicutes)的比值下降,党参干预使其增加;在此过程,主要差异变化的代谢物是脂质及类脂分子、有机酸及其衍生物等,代谢通路有半乳糖代谢、甘油脂代谢、药物代谢-细胞色素P450;组学关联分析显示,Parabacteroides、Lactobacillus和Lachnoclostridium均与脂质及类脂分子密切相关。结论党参水提物对衰老小鼠肠道组织结构和功能有显著保护作用,通过对肠道菌群结构及其代谢物的调节,改善肠道屏障功能,延缓机体衰老。
Objective To reveal the protective effects of Dangshen(Codonopsis pilosula)water extract on intestinal barrier and microbial metabolism in aging model mice.Methods Fifty specific pathogen free(SPF)grade 8-week-old C57BL/6 mice were randomly divided into 5 groups to construct a D-galactose mouse aging model,and different doses of Dangshen(Codonopsis pilosula)water extract were used for intervention.Biochemical analysis was used to detect the levels of superoxide dismutase(SOD),malondialdehyde(MDA)and lipid peroxidation(LPO)in mouse serum.Haematoxylin Eosin(HE)staining was used to observe pathological changes in mouse intestinal tissue.Immunohistochemical staining was used to observe the expressions of Occludin and Claudin 1 proteins in mouse intestinal tissue.The ultrastructure of mouse intestinal tissue cells was observed by using transmission electron microscopy.The combination of 16SrDNA sequencing and metabolomics analysis was used to detect the changes in gut microbiota and metabolites in mice after aging and Dangshen(Codonopsis pilosula)intervention,while joint analysis was conducted through bioinformatics.Results Compared with those of the normal control group,the weight and food intake of aging mice decreased(P<0.05),and the weight and food intake of the intervention group with Dangshen(Codonopsis pilosula)significantly increased compared to those of the aging group(P<0.05).Compared with those in the normal control group,the serum SOD in the aging group decreased(P<0.05),while the levels of MDA and LPO increased(P<0.05).The intervention group with Dangshen(Codonopsis pilosula)significantly reversed the level change of SOD,MDAand LPO(P<0.05).The intestinal tissue structure of aging model mice was significantly damaged,and the expressions of Occludin and Claudin 1 proteins decreased significantly compared to those of the normal controls(P<0.05).After high-dose intervention with Dangshen(Codonopsis pilosula),there was a significant improvement in intestinal tissue damage,and the expressions of Occludin and Claudin 1 proteins increased significantly(P<0.05),and the ultrastructure of mouse intestinal cells tended to be normal.During the aging process of mice,the ratio of Bacteroidota to Firmicutes was decreased,after high-dose intervention with Dangshen(Codonopsis pilosula),the ratio was increased.During this process,the main differential metabolites were lipids and lipid molecules,organic acids and their derivatives.Metabolic pathways included galactose metabolism,glyceride metabolism and drug metabolism-cytochrome P450.Omics association analysis showed that Paraacteroides,Lactobacillus and Lachnochlostrium were closely related to lipids and lipid molecules.Conclusion Dangshen(Codonopsis pilosula)water extract has a significant protective effect on the in-testinal tissue structure and function of aging mice.By regulating the intestinal microbiota structure and its metabolites,it improves the intestinal barrier function and resists aging in the body.