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薛春芳,高少明,吴之易,牟新.基于粪便代谢组学研究肾消方颗粒治疗2型糖尿病肾病患者的作用机制[J].浙江中西医结合杂志,2025,35(5):
基于粪便代谢组学研究肾消方颗粒治疗2型糖尿病肾病患者的作用机制
投稿时间:2025-01-15  修订日期:2025-03-07
DOI:
中文关键词:  2型糖尿病  糖尿病肾病  代谢组学  肾消方
英文关键词:Type 2 Diabetes Mellitus  Diabetic Kidney Disease  Metabolomics  Shenxiao formula
基金项目:]浙江省自然科学基金资助(LY21H270002)。
作者单位E-mail
薛春芳 浙江中医药大学 1807376369@qq.com 
高少明   
吴之易   
牟新* 杭州市红十字会医院 mouxin888@126.com 
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中文摘要:
      目的:探究肾消方颗粒剂对2型糖尿病肾脏疾病(T2DKD)患者粪便代谢物结构的改善作用及其中可能的作用机制。方法:本研究将40例T2DKD患者分为对照组和试验组,均接受标准降糖治疗,试验组加用肾消方。收集治疗前后血液、尿液、粪便样本,测定相关指标。超高效液相色谱和质谱分析方法分析治疗前后粪便差异代谢产物并采集图谱;Compound Discoverer软件提取和预处理代谢数据;SIMCA(V14.1)软件进行成分分析、正交偏最小二乘法-判别分析,筛选差异代谢物,KEGG数据库分析代谢通路并进行富集分析。结果:治疗7天后,两组患者FPG、UACR均显著改善,其中试验组在Scr、Ccr改善上优于对照组(p<0.05)。KEGG数据库分析显示:对照组主要涉及戊糖和葡萄糖醛酸代谢、氨基糖和核苷酸糖代谢、亚油酸代谢等9条代谢通路,显著差异代谢物有D-木糖、γ-亚麻酸、8-乙基-12-甲基氯氯化杆菌D等8种。试验组主要涉及β-丙氨酸代谢、α-亚麻酸代谢、谷胱甘肽代谢等11条代谢通路,显著差异代谢物有L-谷氨酰胺、精胺、3-氨基丙腈等18种。结论:肾消方较普通治疗可显著改善患者Scr、Ccr,可能涉及增强β-丙氨酸、α-亚麻酸、组氨酸、D-谷氨酰胺和D-谷氨酸代谢,降低ROS、MDA,提高SOD活性,减少TNF-α表达等途径。
英文摘要:
      Objective:To explore the effect of Shenxiao formular granules on improving the structure of fecal metabolites in patients with Type 2 Diabetic Kidney Disease (T2DKD).Methods:In this study, 40 patients with T2DKD were divided into control group and test group, all receiving standard hypoglycemic treatment with Shenxiao formular in the test group. Blood, urine, and stool samples were collected and relevant indicators were measured. Ultra-efficient liquid chromatography and mass spectrometry analysis analyzed the fecal differential metabolites before and after treatment and collected the map; Compound Discoverer software extracted and processed metabolic data; SIMCA (V14.1) software performed composition analysis, Orthogonal partial least squares-discriminant analysis, screened the differential metabolites, and analyzed the metabolic pathways in KEGG database and performed enrichment analysis.Results:After 7 days of treatment, both groups showed significant improvements in fasting plasma glucose (FPG) and urinary albumin-to-creatinine ratio (UACR), with the treatment group demonstrating superior improvements in serum creatinine (Scr) and creatinine clearance rate (Ccr) compared to the control group (p < 0.05). Analysis using the KEGG database revealed that the control group was primarily associated with 9 metabolic pathways, including metabolism of pentoses and glucuronic acid, amino sugars and nucleotide sugars, and linoleic acid metabolism, with 8 significantly differential metabolites such as D-xylose, γ-linolenic acid, and 8-ethyl-12-methyl chlorochlorobactene D. The test group was mainly involved in 11 metabolic pathways, including β-alanine metabolism, α-linolenic acid metabolism, and glutathione metabolism, with 18 significantly differential metabolites such as L-glutamine, spermine, and 3-aminopropanenitrile.Conclusion:Shenxiao formula treatment significantly ameliorates Scr and Ccr in patients compared to standard care, potentially by upregulating β-alanine, α-linolenic acid, histidine, D-glutamine, and D-glutamate metabolism, reducing ROS and MDA production, enhancing SOD activity, and decreasing TNF-α expression.
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