系统生物学分析揭示升清化浊方调控代谢异常的关联路径  

System Biology Analysis Reveals the Associated Pathway of Shengqing Huazhuo Prescription in Regulating Metabolic Abnormalities

作　　者：周丽[1] 易菲 王丽芳 李蕊 杨琴[1] 宋永贵 陈浩 ZHOU Li;YI Fei;WANG Lifang;LI Rui;YANG Qin;SONG Yonggui;CHEN Hao(School of Computer,Jiangxi University of Chinese Medicine,Nanchang 330004,China;School of Pharmacy,Jiangxi University of Chinese Medicine,Nanchang 330004,China;Experimental Animal Science and Technology Center,Jiangxi University of Chinese Medicine,Nanchang 330004,China;The Affiliated Hospital of Jiangxi University of Chinese Medicine,Nanchang 330006,China)

机构地区：[1]江西中医药大学计算机学院,南昌330004 [2]江西中医药大学药学院,南昌330004 [3]江西中医药大学实验动物科技中心,南昌330004 [4]江西中医药大学附属医院,南昌330006

出　　处：《中国药学杂志》2024年第19期1813-1824,共12页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金项目资助(82360966);江西省教育厅科学技术研究项目资助(GJJ2200959);江西省卫生健康委员会科技计划项目资助(202211433);大学生创新创业训练计划项目资助(202310412024);江西中医药大学大学生创新创业训练计划项目资助(X202310412274)。

摘　　要：目的 探讨升清化浊方调控大鼠脾虚湿阻型单纯性肥胖的作用机制。方法 建立脾虚湿阻型单纯性肥胖大鼠模型,综合评价升清化浊方对肥胖大鼠体质量、肝脏组织形态学以及血脂代谢表达水平的影响。利用超高效液相色谱-四级杆静电场轨道阱质谱法(ultra high performance liquid chromatography-Q/Exactive mass spectrometry, UHPLC-QE-MS)联用技术,鉴定升清化浊方的入血成分,并通过网络药理学平台预测其潜在作用靶点和通路。同时,采用非靶向代谢组学对大鼠血清进行代谢组学分析。通过16S rDNA扩增子测序技术,对大鼠粪便中的肠道菌群丰度进行检测。最后,对三者的KEGG通路汇总,构建了一个多尺度、多维度网络,用于整体可视化和深度分析。结果 升清化浊方给药后显著降低了肥胖大鼠的体质量,同时改善了血脂水平和肝脏脂肪蓄积情况。通过UHPLC-QE-MS技术鉴定了升清化浊方中的27个入血成分。网络药理学分析揭示了升清化浊方与代谢相关的通路,主要涉及到类固醇激素生物合成和卵巢类固醇生成等。血清代谢组学分析得到了10个关键差异代谢物,其涉及到的代谢途径是不饱和脂肪酸的生物合成、色氨酸代谢等。肠道菌群测序结果显示,升清化浊方能够调节肥胖大鼠的肠道菌群组成并改善结构,其涉及到的代谢途径是类固醇激素、不饱和脂肪酸的生物合成。结论 升清化浊方不仅在治疗大鼠脾虚湿阻型单纯性肥胖方面表现出显著疗效,还具备调节血清代谢和肠道微生物群落结构的能力。OBJECTIVE To explore the mechanism of Shengqing Huazhuo(SQHZ)prescription in regulating simple obesity rats with spleen deficiency and dampness obstruction.METHODS The rat model of simple obesity with spleen deficiency and dampness obstruction was established,and the effects of SQHZ prescription on body weight,liver histomorphology and expression level of blood lipid metabolism in obesity rats were comprehensively evaluated.Ultra-high performance liquid chromatography-Q/Exactive mass spectrometry(UHPLC-QE-MS)was used to identify the blood components of SQHZ prescription,and the potential action pathways and targets were predicted by the network pharmacological platform.Non-targeted metabonomics was used to analyze the metabolomics of rat serum.The abundance of intestinal flora in rat faeces was detected by 16S rDNA amplicon sequencing technology.Finally,a multi-scale and multi-dimensional network was constructed by summarizing the KEGG pathways of the three,which can be used for overall visualization and deep analysis.RESULTS SQHZ prescription significantly reduced the body weight of obesity rats,and improved blood lipid levels and liver fat accumulation.Twenty-seven blood components of SQHZ prescription were identified by UHPLC-QE-MS technology.Network pharmacological analysis revealed the pathways related to metabolism of SQHZ prescription,mainly involving steroid hormone biosynthesis and ovarian steroidogenesis.Serum metabolomics analysis obtained 10 key differential metabolites,which involved metabolic pathways such as biosynthesis of unsaturated fatty acids and tryptophan metabolism.Intestinal microbiota sequencing results showed that SQHZ prescription could regulate the composition and improve the structure of intestinal microbiota in obesity rats,and the metabolic pathways involved are the biosynthesis of steroid hormones and unsaturated fatty acids.CONCLUSION SQHZ prescription not only shows significant therapeutic effects in treating simple obesity rats with spleen deficiency and dampness obstruction,but

关 键 词：血清药物化学 超高效液相色谱-四级杆静电场轨道阱质谱法 升清化浊方 血清代谢组学 肠道菌群 

分 类 号：R963[医药卫生—微生物与生化药学]