河南中医药大学;
目的：基于非靶代谢组学探讨荣肝复方对CCL_4诱导的肝纤维化模型小鼠的干预机制，为荣肝复方治疗肝纤维化提供科学依据。方法：将30只小鼠随机分为3组，分别为对照组、模型组、荣肝复方组。首先建立CCL_4诱导的肝纤维化小鼠模型，在此基础上采用荣肝复方干预15 d后，取肝脏组织进行非靶向代谢组学及相关生物信息分析。运用UPLC-MS技术检测各组小鼠肝脏组织代谢组学变化，确定与荣肝复方作用机制密切相关的代谢途径。结果：在慢性肝损伤发病过程中，与对照组相比，模型组小鼠肝脏组织在阳离子模式和阴离子模式下分别检测出323、152个差异代谢物。与模型组相比，荣肝复方组小鼠肝脏组织在阳离子模式和阴离子模式下分别检测出235、130个差异代谢物。阳离子模式下，对3组小鼠肝脏组织样本进行趋势分析，有2个代谢物群具有显著趋势变化，分别表现为先上升后保持平稳和先下降后保持平稳。阴离子模式下，有2个代谢物群具有显著趋势变化，分别表现为先上升后下降和先下降后上升。代谢集富集到的相关通路说明，CCl_4诱导小鼠慢性肝损伤机制和荣肝复方干预机制与胰岛素抵抗、胰高血糖素信号通路、癌症中的中心碳代谢、代谢途径、不饱和脂肪酸的生物合成、ABC转运蛋白、精氨酸和脯氨酸代谢、脂肪细胞脂解的调控、蛋白质消化吸收等通路有关。尤其是ABC转运蛋白、脂肪酸代谢和胰岛素抵抗的调控尤其显著。结论：荣肝复方主要通过调控ABC转运蛋白、脂肪酸代谢和胰岛素抵抗等通路，缓解CCl_4导致的小鼠肝损伤。
| 456 | 1 | 12 |
| 下载次数 | 被引频次 | 阅读次数 |
[1]XU H M,YANG N,ZHANG Z Q,et al.Expression of matrix metalloproteinase-2,tissue inhibitor of matrix metalloproteinase-2 and CD147 in the traditional Chinese medicine "compound T11" for treatment of chronic liver injury[J].Pharmacology,2019,103(3/4):128-135.
[2]杨念，徐华明，胡文文，等.一种治疗慢性肝损伤的中药组合物[J].中国中医药现代远程教育，2017,15(23):148-150.
[3]杨念，张振强，杨文胜，等.一种中药组合物治疗慢性肝损伤的药效学研究[J].社区医学杂志，2018,16(5):78-80.
[4]江明珠，王淑惠，王竟先，等.基于肝脏代谢组学研究柴胡皂苷A对小鼠酒精性脂肪肝保护作用[J].中国现代中药，2023,25(12):2528-2539.
[5]GONG X H,ZHANG F,LI Y X,et al.Study on the mechanism of acute liver injury protection in Rhubarb anthraquinone by metabolomics based on UPLC-Q-TOF-MS[J].Front Pharmacol,2023,14:1141147.
[6]QIN X,WANG Y,MACKENZIE K R,et al.Identifying the reactive metabolites of tyrosine kinase inhibitor pexidartinib in vitro using LC-MS-based metabolomic approaches[J].Chem Res Toxicol,2023,36(8):1427-1438.
[7]CHU Y,ZHANG Y,LIU J,et al.An integrated liver,hippocampus and serum metabolomics based on UPLC-Q-TOF-MS revealed the therapeutical mechanism of Ziziphi Spinosae Semen in p-chlorophenylalanine-induced insomnia rats[J].Biomed Chromatogr,2024,38(3):e5796.
[8]BERTRAN L,CAPELLADES J,ABELLO S,et al.LC/MS-based untargeted metabolomics study in women with nonalcoholic steatohepatitis associated with morbid obesity[J].Int J Mol Sci,2023,24(12):9789.
[9]王志博，蔡莹，郭思凡，等.基于代谢组学方法的中药药效及物质基础的研究进展[J].药物评价研究，2023,46(9):2024-2029.
[10]陈思敏，黄锦豪，王德勤，等.基于代谢组学及分子对接技术揭示消炎利胆方干预慢性肝内胆汁淤积的作用机制[J].药学学报，2023,58(11):3408-3420.
[11]SAGI-KISS V,LI Y F,CAREY M R,et al.Ion-pairing chromatography and amine derivatization provide complementary approaches for the targeted LC-MS analysis of the polar metabolome[J].J Proteome Res,2022,21(6):1428-1437.
[12]CRIZER D M,RAMAIAHGARI S C,FERGUSON S S,et al.Benchmark concentrations for untargeted metabolomics versus transcriptomics for liver injury compounds in in vitro liver models[J].Toxicol Sci,2021,181(2):175-186.
[13]WU J,LUO Y,SHEN Y,et al.Integrated metabonomics and network pharmacology to reveal the action mechanism effect of Shaoyao decoction on ulcerative colitis[J].Drug Des Devel Ther,2022,27(16):3739-3776.
[14]DENG S,CAI K W,PEI C Y,et al.16S rRNA and metagenomics combined with UPLC-Q/TOF-MS metabolomics analysis reveals the potential mechanism of Radix astragali against hyperuricemia in mice[J].Drug Des Devel Ther,2023,17:1371-1386.
[15]PIANO S,CARDENAS A.Metabolomics to predict acute kidney injury in cirrhosis[J].Hepatology,2021,74(5):2339-2341.
[16]WANG L,DONG X L,QIN X M,et al.Investigating the inter-individual variability of Astragali Radix against cisplatin-induced liver injury via 16S rRNA gene sequencing and LC/MS-based metabolomics[J].Phytomedicine,2022,101:154107.
[17]ZHANG X,ZHAO F,MA T,et al.UPLC-Q-TOF/MS-based metabonomics reveals mechanisms for Holothuria leucospilota polysaccharides (HLP)-regulated serum metabolic changes in diabetic rats[J].Food Chem X,2023,19:100741.
[18]WANG Q,LUO Z,LI D,et al.Investigation of the therapeutic effect of total alkaloids of corydalis saxicola bunting on CCl4-induced liver fibrosis in rats by LC/MS-based metabolomics analysis and network pharmacology[J].Metabolites,2022,21;13(1):9.
[19]WU C,XING X,LIU G,et al.Effects of Nongxiangxing baijiu (Chinese liquor) on mild alcoholic liver injury revealed by non-target metabolomics using ultra-performance liquid chromatography quadrupole-time-of-flight mass spectrometry[J].J Biosci Bioeng,2022,134(1):62-69.
[20]BI D,SHI M,HU Q W,et al.LC/MS/MS-based liver metabolomics to identify chronic liver injury biomarkers following exposure to arsenic in rats[J].Biol Trace Elem Res,2022,200(10):4355-4369.
基本信息:
DOI：10.16368/j.issn.1674-8999.2024.10.358
中图分类号:R285.5
引用信息:
[1]杨念,杨柳,郑思嘉等.基于非靶代谢组学探讨荣肝复方对小鼠慢性肝纤维化的干预机制[J].中医学报,2024,39(10):2176-2184.DOI:10.16368/j.issn.1674-8999.2024.10.358.
基金信息:
河南省中医药科学研究专项项目(2024ZY1030,20-21ZY1055); 河南省科技攻关规划项目(232102310473); 河南中医药大学科研苗圃工程项目(MP2022-17)