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作 者:张强[1] 罗曦 韩丽颖 王帅[1,2,3] 包永睿 李天娇[1,2,3] 孟宪生 ZHANG Qiang;LUO Xi;HAN Liying;WANG Shuai;BAO Yongrui;LI Tianjiao;MENG Xiansheng(School of Pharmacy,Liaoning University of Traditional Chinese Medcine,Dalian 116600,China;Professional InnovationTechnology Center for Multidimensional Analysis of Traditional Chinese Medicine,Dalian 116600,China;Liaoning ProvinceModern Chinese Medicine Research Engineering Laboratory,Dalian 116600,China)
机构地区:[1]辽宁中医药大学药学院,大连116600 [2]辽宁省中药多维分析专业创新技术中心,大连116600 [3]辽宁省现代中药研究工程实验室,大连116600
出 处:《中华中医药杂志》2024年第10期5481-5487,共7页China Journal of Traditional Chinese Medicine and Pharmacy
基 金:辽宁省中医药现代化研究创新团队项目(No.LT2017015)。
摘 要:目的:基于代谢组学研究人脐带间充质干细胞(hUC-MSCs)来源的外泌体(hUC-MSCs-Exos)联合复方木鸡颗粒抑制人肝癌细胞SMMC-7721增殖机制。方法:采用hUC-MSCs提取外泌体,通过检测复方木鸡颗粒、外泌体以及联合给药对人肝癌细胞SMMC-7721的增殖抑制率,验证联合给药前后的药效差异;检测糖酵解、炎症、氧化应激等通路上的关键靶点;采用细胞代谢组学结合UPLC-Q-TOF-MS技术研究其作用机制。结果:复方木鸡颗粒可显著抑制人肝癌细胞SMMC-7721的增殖,外泌体抑制效果不明显,但二者联合应用效果增强。复方木鸡颗粒与外泌体联合前后均可回调多条通路上的靶点。结论:复方木鸡颗粒与hUC-MSCs-Exos联合后药效增强机制可能与赖氨酸降解、脂肪酸降解、脂肪酸伸长率、氮代谢、咖啡因代谢等有关。Objective:To investigate the mechanism of human umbilical cord mesenchymal stem cells(hUC-MSCs)derived exosomes(hUC-MSCs-Exos)combined with Compound Muji Granules on the proliferation and apoptosis of human liver cancer cell line SMMC-7721 based on metabolomics.Methods:Exosomes were extracted from hUC-MSCs.The proliferation inhibition rate and apoptosis necrosis of human liver cancer cell line SMMC-7721 were detected by detecting the Compound Muji Granules,extracellular vesicles,and combined administration,to verify the efficacy differences before and after combined administration.Key targets in pathways such as glycolysis,inflammation,and oxidative stress were detected by ELISA.The mechanism of action was studied by using cell metabolomics combined with UPLC-Q-TOF-MS technology.Results:Compound Muji Granules can significantly inhibit the proliferation of human liver cancer cell line SMMC-7721,and the inhibitory effect of exosomes is not significant,but the combined application of the two has an enhanced effect.The combination of Compound Muji Granules and exosomes can recall targets on multiple pathways before and after treatment.Conclusion:The mechanism of enhanced efficacy of Compound Muji Granules combined with hUC-MSCs-Exos may be related to lysine degradation,fatty acid degradation,fatty acid elongation,nitrogen metabolism,caffeine metabolism.
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