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基于微生物组-代谢组学探讨尿毒清颗粒对大鼠慢性肾脏病的改善作用及其机制

[Effect of Uremic Clearance Granules on improvement of chronic kidney disease in rats based on microbiome-metabolomics and its mechanism].

作者信息

Xu Ya-Qin, Huang Yao-Min, He Meng-Ying, Chu Fu-Jiang

机构信息

Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances Guangzhou 510006, China School of Life Science and Biopharmaceutics, Guangdong Pharmaceutical University Guangzhou 510006, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2023 Jan;48(1):160-169. doi: 10.19540/j.cnki.cjcmm.20220901.401.

Abstract

This research aimed to study the effect of Uremic Clearance Granules on chronic kidney disease in SD rats by using the methods of microbial functional genomics combined with metabolomics, and to preliminarily explore its mechanism. The SD rat model of chronic kidney disease was established by the adenine-induced method. After the model was successfully induced, the animals were randomly divided into a negative control group, a Uremic Clearance Granule treatment group, and a normal control group, with 8 rats in each group. After 4 weeks of administration, animal feces and serum were collected, and 16S rDNA sequencing technology was used to analyze the abundance, diversity, and function prediction of intestinal microorganisms. Liquid chromatography-mass spectrometry(LC-MS) technology was used to perform high-throughput sequencing to detect animal serum metabolites. The MetPA database was used to screen out potential biomarkers of chronic kidney disease in rats and conduct the enrichment analysis of metabolic pathways. Spearman's method was used to analyze the correlation between the two omics. The results showed that Uremic Clearance Granules effectively improved the body weight loss and renal function-related biochemical and appearance indicators in rats with chronic kidney disease. The results of 16S rDNA sequencing showed that Uremic Clearance Granules regulated the diversity and composition of the intestinal flora in rats with chronic kidney disease. The changes in the intestinal flora affected functional metabolic pathways such as amino acid biosynthesis and metabolism, lipid metabolism, and carbohydrate metabolism. The results of LC-MS showed that as compared with the negative control group, 15 metabolites were reversed in the Uremic Clearance Granule treatment group, among which 11 potential marker metabolites were significantly up-regulated and 4 potential marker metabolites were significantly down-regulated. Five amino acid metabolic pathways were mainly involved, which were significantly correlated with changes in the intestinal flora. Therefore, Uremic Clearance Granules can improve the renal function of rats with chronic kidney disease, and the mechanism may be related to its effect on the amino acid metabolism pathway by regulating the intestinal flora.

摘要

本研究旨在采用微生物功能基因组学与代谢组学相结合的方法,研究尿毒清颗粒对SD大鼠慢性肾脏病的影响,并初步探讨其作用机制。采用腺嘌呤诱导法建立SD大鼠慢性肾脏病模型。模型成功诱导后,将动物随机分为阴性对照组、尿毒清颗粒治疗组和正常对照组,每组8只大鼠。给药4周后,收集动物粪便和血清,采用16S rDNA测序技术分析肠道微生物的丰度、多样性及功能预测。采用液相色谱-质谱联用(LC-MS)技术进行高通量测序,检测动物血清代谢产物。利用MetPA数据库筛选大鼠慢性肾脏病潜在生物标志物,并进行代谢通路富集分析。采用Spearman法分析两组组学之间的相关性。结果显示,尿毒清颗粒有效改善了慢性肾脏病大鼠的体重减轻及肾功能相关生化指标和外观指标。16S rDNA测序结果表明,尿毒清颗粒调节了慢性肾脏病大鼠肠道菌群的多样性和组成。肠道菌群的变化影响了氨基酸生物合成与代谢、脂质代谢和碳水化合物代谢等功能代谢通路。LC-MS结果显示,与阴性对照组相比,尿毒清颗粒治疗组有15种代谢产物发生逆转,其中11种潜在标志物代谢产物显著上调,4种潜在标志物代谢产物显著下调。主要涉及5条氨基酸代谢通路,与肠道菌群变化显著相关。因此,尿毒清颗粒可改善慢性肾脏病大鼠的肾功能,其机制可能与其通过调节肠道菌群影响氨基酸代谢通路有关。

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