网络药理学结合高通量测序研究驻景丸对高脂饮食小鼠肠黏膜菌群的影响  

Effect of Zhujing Pill on intestinal mucosal flora in mice fed with high-fat diet by network pharmacology combined with high-throughput sequencing

作　　者：刘琴 周梦思 谭周进 邓娜 LIU Qin;ZHOU Mengsi;TAN Zhoujin;DENG Na(College of Traditional Chinese Medicine,Hu′nan University of Chinese Medicine,Changsha,Hu′nan 410208,China;不详)

机构地区：[1]湖南中医药大学中医学院,湖南长沙410208

出　　处：《中国微生态学杂志》2025年第1期29-36,共8页Chinese Journal of Microecology

基　　金：湖南省自然科学基金青年科学基金(2024JJ6346);湖南省教育厅优秀青年基金(23B0348)。

摘　　要：目的采用网络药理学和16S rRNA基因测序探讨驻景丸对高脂饮食小鼠肠道黏膜菌群和体重的影响。方法25只4周龄体重18~22 g的SPF级雄性C57BL/6小鼠被随机分为正常组(CC组,n=5)和造模组(n=20),造模组予高脂饲料喂养12周。造模结束后,选取造模成功小鼠随机分为模型组(HF组,n=5)和驻景丸组(ZJP组,n=5),ZJP组给予驻景丸水煎液,1.10 g/mL,1次/d,连续4周,其余两组灌胃等量无菌水。采集肠道黏膜,以16S rRNA基因测序分析肠道菌群。同时运用网络药理学分析驻景丸干预黄斑变性的关键靶点。结果网络药理学分析显示驻景丸可以调节86个与肥胖相关的靶点,进一步PPI网络分析、KEGG富集分析显示驻景丸治疗黄斑变性的途径与降脂相关(脂质和动脉粥样硬化、糖尿病并发症中AGERAGE信号通路、流体剪切应力与动脉粥样硬化)。体重结果显示,与CC组相比,造模各组小鼠体重显著上升,驻景丸干预后高脂饮食小鼠的体重恢复至正常水平。测序结果显示,alpha多样性分析中Ace指数和Chao1指数差异均无统计学意义(F=1.262、0.949,P=0.318、0.414);与CC组相比,ZJP组小鼠的Simpson指数和Shannon指数均升高(t=3.599、3.110,P=0.007、0.014)。Beta多样性分析显示,与HF组相比,ZJP组与CC组距离较近;驻景丸干预后,与HF组相比,ZJP组Proteobacteria的相对丰度降低(t=2.489,P<0.038),uncultured bacterium f Enterobacteriaceae的相对丰度增加(t=3.076,P=0.015)。LEfSe分析显示,uncultured bacterium f Cryomorphaceae、Lachnospiraceae NK4A136 group、uncultured bacterium f Lachnospiraceae、Romboutsia、Faecalibacterium、uncultured bacterium f Ruminococcaceae、Ochrobactrum、uncultured bacterium f Enterobacteriaceae和Treponema 2为ZJP组的优势菌属。相关性分析结果显示,驻景丸给药后体重与uncultured bacterium f Cryomorphacea呈显著负相关(r=−0.7165,P=0.038)。结论驻景丸能改变肠道菌群的群落结构,增加黏膜菌群的丰富度和多Objective To explore the effect of Zhujing Pill on intestinal mucosal flora and body weight of mice fed with high-fat diet by using network pharmacology and 16S rRNA gene sequencing.Methods Twenty-five SPF male C57BL/6 mice were randomly divided into normal group(CC group,n=5)and model group(n=20).The model group was fed with high-fat feed for 12 weeks.After modeling,the successfully modeled mice were randomly divided into model group(HF group,n=5)and Zhujing Pill group(ZJP group,n=5).The ZJP group was given Zhujing Pill decoction,1.10 g/mL qd for 4 weeks,and the other two groups were given the same amount of sterile water.The intestinal mucosa was collected and the intestinal flora was analyzed with 16S rRNA gene sequencing.Network pharmacology was used to analyze the key targets of Zhujing Pill in intervening macular degeneration.Results Network pharmacological analysis showed that Zhujing Pill could regulate 86 obesity-related targets.Further PPI network analysis and KEGG enrichment analysis showed that the treatment of macular degeneration by Zhujing Pill was related to lipid lowering(lipid and atherosclerosis,AGE-RAGE signaling pathway in diabetic complications,fluid shear stress and atherosclerosis).The weight results showed that compared with CC group,the weight of mice in each model group increased significantly,and the weight of mice fed with high-fat diet returned to normal level after the intervention of Zhujing Pill.The sequencing results showed that there were no significant differences in Ace index and Chao1 index in alpha diversity analysis(F=1.262,P=0.318;F=0.949,P=0.414).Compared with CC group,the Simpson index and Shannon index in ZJP group increased(t=3.599,P=0.007;t=3.110,P=0.014).Beta diversity analysis showed that compared with HF group,ZJP group was closer to CC group.After the intervention of Zhujing Pill,compared with HF group,the relative abundance of Proteobacteria in ZJP group decreased(t=2.489,P<0.038),while the relative abundance of uncultured bacterium f Enterobacteriaceae in ZJP gr

关 键 词：驻景丸 高脂饮食 肠道菌群 肠道黏膜 网络药理学 

分 类 号：R289[医药卫生—方剂学]