基于UHPLC-MS/MS代谢组学探讨金匮肾气丸对慢性肾病肾间质纤维化的改善作用及其机制研究OA
Effects and Mechanisms of Jingui Shenqi Pills in Ameliorating Renal Interstitial Fibrosis in Chronic Kidney Disease Based on UHPLC-MS/MS Metabolomics
目的:研究金匮肾气丸对慢性肾病肾间质纤维化的药效作用,并利用 UHPLC-MS/MS 代谢组学探讨其潜在作用机制.方法:SD 大鼠随机分成正常对照组、模型对照组、氯沙坦 5 mg/kg 组及金匮肾气丸 0.6、1.2、2.4 g/kg 组,采用腺嘌呤200 mg/kg 灌胃造模,造模3 w,给药 7 w.取材前将大鼠置于代谢笼中收集 24 h 尿液;末次给药1 h 后取材,检测血清尿素氮(BUN)、肌酐(Crea)及尿中 Crea 含量,计算肌酐清除率(CCr);HE 和 Mas-son 染色检测肾脏组织病理损伤;采用 UHPLC-MS/MS 检测血清内源性代谢物.结果:与正常对照组比较,模型对照组血清 BUN、Crea 含量显著升高(P<0.01),CCr 显著降低(P<0.01);与模型对照组相比,金匮肾气丸各组血清BUN、Crea 含量明显降低(P<0.05 或 P<0.01),CCr 显著升高(P<0.01),腺嘌呤致肾小球萎缩,肾小管扩张,细胞排列稀疏,刷状缘消失,炎性细胞浸润及肾间质胶原纤沉积等疾病损伤.代谢组学结果显示,金匮肾气丸调节的差异代谢物有132 个,富集出63 条通路,其中有9 条关键代谢通路.结论:金匮肾气丸能抑制腺嘌呤所致肾间质纤维化,其作用机制可能与氨基酸代谢、脂质代谢和能量代谢相关.
Objective:To investigate the pharmacodynamic effects of Jinkui Shenqi(金匮肾气丸)Pills on renal interstitial fibrosis(RIF)in chronic kidney disease(CKD)and to explore the potential mechanisms using UHPLC-MS/MS metabolomics.Methods:SD rats were randomly divided into a normal control group,a model control group,a Losar-tan group,and Jinkui Shenqi Pills groups at doses of 0.6,1.2,and 2.4 g/kg.CKD was induced by oral administration of adenine(200 mg/kg)for 3 weeks,followed by 7 weeks of drug treatment.Prior to sampling,rats were housed in meta-bolic cages for 24 hours to collect urine.One hour after the last administration,blood samples were collected to measure serum urea nitrogen(BUN)and creatinine(Crea),and urinary Crea was measured to calculate the creatinine clearance rate(CCr).Kidney pathology was assessed using hematoxylin-eosin(HE)and Masson's trichrome staining.Endogenous serum metabolites were analyzed by ultrahigh-performance liquid chromatography coupled with tandem mass spectrometry(UHPLC-MS/MS).Results:Compared with the normal control group,the model group showed significantly increased serum BUN and Crea levels(P<0.01)and significantly decreased CCr(P<0.01).Compared with the model group,Jinkui Shenqi Pills significantly reduced serum BUN and Crea levels(P<0.05 or P<0.01)and markedly increased CCr(P<0.01).Histopathological analysis indicated that Jinkui Shenqi Pills ameliorated adenine-induced renal lesions,in-cluding glomerular atrophy,renal tubular dilation,sparse cellular arrangement,loss of brush borders,inflammatory cell in-filtration,and collagen fiber deposition in the renal interstitium.Metabolomic analysis revealed that Jinkui Shenqi Pills modulated 132 differential metabolites and enriched 63 metabolic pathways,among which 9 were identified as key path-ways.Conclusion:Jinkui Shenqi Pills can inhibit adenine-induced renal interstitial fibrosis,and its mechanism may be related to the regulation of amino acid metabolism,lipid metabolism,and energy metabolism.
李安;陈云贵;谢高宇;晋海军;梁建东;杨芳芳;蔡琨;刘琴;王丽颖
贵州中医药大学,贵阳 550025贵州中医药大学,贵阳 550025贵州中医药大学,贵阳 550025贵州中医药大学,贵阳 550025贵州中医药大学,贵阳 550025贵州省药品监督管理局检查中心,贵阳 550081贵州中医药大学,贵阳 550025贵阳市公共卫生救治中心,贵阳 550004贵州省药品监督管理局检查中心,贵阳 550081
金匮肾气丸慢性肾病肾间质纤维化代谢组学肾功能
Jinkui Shenqi PillsChronic kidney diseaseRenal interstitial fibrosisMetabolomicsRenal function
《中药药理与临床》 2026 (3)
10-17,8
贵州中医药大学学术新苗项目(贵科合学术新苗[2023]-29号)贵州省科协"新质黔沿"引领项目(编号:2025XZQYXM-02-04)贵州省科技创新人才团队(黔科合平台人才[2020]5010)贵州省发改委工程研究中心建设项目(黔发改高技[2020]896号)贵州省苗医药全省重点实验室(黔科合平台ZSYS[2025]018).
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