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基于超高效液相色谱-四极杆飞行时间串联质谱法研究山茱萸酒制前后与黄芪配伍对糖尿病肾病大鼠血浆代谢组学的影响

[Effect of compatibility of Corni Fructus before and after wine-processing with Astragali Radix on plasma metabolomics in diabetic nephropathy rats based on UHPLC-Q-TOF-MS/MS].

作者信息

Chen Yi-Jing, Zhu Hui, Liu Xin, Duan Yu, Pei Ke, Zhang Qiao, Song Pei-Xiang, Cai Hao

机构信息

School of Pharmacy, Nanjing University of Chinese Medicine Nanjing 210023, China Engineering Center of State Ministry of Education for Standardization of Chinese Medicine Processing,Nanjing University of Chinese Medicine Nanjing 210023, China.

School of Chinese Medicine and Food Engineering, Shanxi University of Chinese Medicine Jinzhong 030619, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2024 Jul;49(13):3493-3504. doi: 10.19540/j.cnki.cjcmm.20240319.302.

DOI:10.19540/j.cnki.cjcmm.20240319.302
PMID:39041121
Abstract

Based on the processing and compatibility, this study explored the effects of components in Corni Fructus(CF) and Astragali Radix(AR) on plasma metabolomics in diabetic nephropathy rats. SD rats were randomly divided into four groups and diabetic nephropathy rat model was induced by high-fat diet combined with 30 mg·kg~(-1) streptozotocin(STZ). Histopathological observations of kidney tissue sections of rats in each group were conducted using HE, PAS, and Masson staining. Ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry(UHPLC-Q-TOF-MS/MS) metabolomics method was employed to investigate the effects of CF before and after wine-processing combined with AR-related components on plasma metabolites in diabetic nephropathy rats. After drug treatment, kidney tissue damage and interstitial collagen fiber deposition area in diabetic nephropathy rats were improved to varying degrees(P<0.001). The detection results of plasma metabolomics showed that 71 biomarkers related to the pathogenesis of diabetic nephropathy were identified in diseased rats, mainly involving linoleic acid metabolism, caffeine metabolism, glycerophospholipid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arachidonic acid metabolism, phenylalanine metabolism, retinol metabolism, and ether lipid metabolism. After drug intervention, 26 of them were significantly downregulated, with better efficacy observed in precision processed herb-pair group(P-CG_5). This study elucidated from the perspective of plasma metabolomics that P-CG_5 could improve metabolic disorders in diabetic nephropathy through pathways such as phenylalanine, tyrosine and tryptophan biosynthesis, phenylalanine metabolism, and caffeine metabolism, providing theoretical support and experimental basis for the clinical application of CF and AR compatibility in traditional Chinese medicine.

摘要

基于炮制与配伍,本研究探讨山茱萸(CF)和黄芪(AR)中的成分对糖尿病肾病大鼠血浆代谢组学的影响。将SD大鼠随机分为四组,采用高脂饮食联合30mg·kg⁻¹链脲佐菌素(STZ)诱导建立糖尿病肾病大鼠模型。对每组大鼠肾组织切片进行HE、PAS和Masson染色,进行组织病理学观察。采用超高效液相色谱-四极杆飞行时间串联质谱(UHPLC-Q-TOF-MS/MS)代谢组学方法,研究酒制前后的CF与AR相关成分对糖尿病肾病大鼠血浆代谢产物的影响。药物治疗后,糖尿病肾病大鼠肾组织损伤及间质胶原纤维沉积面积均有不同程度改善(P<0.001)。血浆代谢组学检测结果显示,在患病大鼠中鉴定出71种与糖尿病肾病发病机制相关的生物标志物,主要涉及亚油酸代谢、咖啡因代谢、甘油磷脂代谢、苯丙氨酸、酪氨酸和色氨酸生物合成、花生四烯酸代谢、苯丙氨酸代谢、视黄醇代谢和醚脂代谢。药物干预后,其中26种显著下调,精准配伍组(P-CG_5)疗效更佳。本研究从血浆代谢组学角度阐明,P-CG_5可通过苯丙氨酸、酪氨酸和色氨酸生物合成、苯丙氨酸代谢和咖啡因代谢等途径改善糖尿病肾病的代谢紊乱,为中药CF与AR配伍的临床应用提供理论支持和实验依据。

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