目的 通过网络药理学和16S rRNA基因测序探究滋阴明目汤干预高脂饮食诱导肥胖小鼠体重和肠道黏膜菌群的影响。方法 采用网络药理学预测滋阴明目汤一黄斑变性的潜在功能,将25只4周龄18~22g的SPF级雄性C57BL/6小鼠随机分为正常组(CN组,5只)和造模组(20只),造模组小鼠予高脂饲料喂养12周。造模结束后,选取造模成功小鼠随机分为模型组(HF组,5只)和滋阴明目汤组(ZYMM组,5只),ZYMM组小鼠以滋阴明目汤干预4周,其余两组灌胃等量无菌水。收集各组小鼠肠道黏膜,高通量测序分析菌群。结果 网络药理学分析得到滋阴明目汤一黄斑变性存在糖尿病心肌病、胰岛素抵抗、流体切应力和动脉粥样硬化以及糖尿病并发症中的AGE-RAGE信号通路等与降脂作用相关的通路。滋阴明目汤干预后,高脂饮食小鼠体重下降。HF组小鼠肠道黏膜菌群中OTU数和alpha多样性均较高。相较于HF组,ZYMM组和CN组小鼠肠道黏膜菌群beta多样性距离较近。Escherichia-Shigella和Lachnospiraceae NK4A136 group 差异显著,结合 LEfSe 分析,HF 组富集 Escherichia-Shigella,ZYMM 组富集 uncultured bacterium f Lach-nospiraceae 和Lachnospiraceae NK4A136 group。相关性分析表明,滋阴明目汤给药后小鼠体重与uncultured bacterium f Muribaculaceae 和 Desulfovibrio 丰度呈负相关,同时与 uncultured bacterium c subgroup 6 丰度呈正相关。结论 滋阴明目汤干预后高脂饮食小鼠的肠道致病菌数量下降,有益菌数量增加,其机制主要通过影响 Escherichia-Shigella、Desulfovibrio、uncultured bacterium f Muribaculaceae 和 Lachnospiraceae NK4A136 group 改善高脂饮食小鼠肠道微生态,降低体重。
The effect of Ziyin Mingmu decoction on intestinal mucosal flora in mice fed with high-fat diet based on network pharmacology
Objective To observe the effects of Ziyin Mingmu(nourishing yin and brightening eyes)decoction on body weight and intestinal mucosal flora in obese mice induced by high-fat diet.Methods Network pharmacology was used to predict the potential function of Ziyin Mingmu decoction in the treatment of macular degeneration.SPF male C57BL/6 mice were randomly divided into normal control group(CN group,n=5)and model group(n=20),and the model group was fed with high-fat feed for 12 weeks.After successful modeling,the mice were randomly divided into model group(HF group,n=5)and Ziyin Mingmu decoction group(ZYMM group,n=5).The ZYMM group was intervened with Ziyin Ming-mu decoction for 4 weeks,and the other two groups were given the same amount of sterile water.The intestinal mucosa of mice in each group was collected,and the intestinal mucosal flora was analyzed using high-throughput sequencing tech-nique.Results According to the analysis of network pharmacology,the pathways Ziyin Mingmu decoction treating macu-lar degeneration were related to lipid-lowering such as the AGE-RAGE signaling pathway in diabetic cardiomyopathy,in-sulin resistance,fluid shear stress and atherosclerosis,and in diabetic complications.The weights of mice fed with high-fat diet reduced after the administration of Ziyin Mingmu decoction.The diversity of OTU and alpha diversity in intestinal mu-cosal flora in HF group was high,and the distance of beta diversity between ZYMM group and CN group was closer com-pared to that in HF group.At the genus level,there was a statistical difference between Escherichia-Shigella and Lachnos-piraceae NK4A136 group.Combined with LEfSe analysis,Escherichia-Shigella was enriched in HF group,while uncul-tured bacteria f Lachnospiraceae and Lachnospiraceae NK4A136 group were enriched in ZYMM group.In the correlation analysis,the body weights of mice after administration of Ziyin Mingmu decoction was negatively correlated with un-cured bacteria f Muribaculaceae and Desulfovibrio,while positively correlated with uncultured bacterium c subgroup 6.Conclusion Ziyin Mingmu decoction intervenes with the decrease of the count of intestinal pathogenic bacteria and the increase of that of beneficial bacteria,and improves intestinal microecology to help reduce weights of mice fed with high-fat diet mainly by influencing Escherichia-Shigella,Desulfovibrio,uncultured bacteria f Muribaculaceae and Lachnospir-aceae NK4A136 group.