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转录组分析揭示复方阿胶浆三种活性成分在小鼠化疗诱导骨髓抑制中的潜在机制

Transcriptome Profiling Analysis Reveals the Potential Mechanisms of Three Bioactive Ingredients of Fufang E'jiao Jiang During Chemotherapy-Induced Myelosuppression in Mice.

作者信息

Li Xue, Zhang Yan, Hong Zhuping, Gong Shuqing, Liu Wei, Zhou Xiangshan, Sun Yangen, Qian Jing, Qu Haibin

机构信息

Pharmaceutical Informatics Institute, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.

National Engineering Research Center for Gelatin-based Traditional Chinese Medicine, Dong-E-E-Jiao Co., Ltd., Liaocheng, China.

出版信息

Front Pharmacol. 2018 Jun 13;9:616. doi: 10.3389/fphar.2018.00616. eCollection 2018.

Abstract

Although multiple bioactive components have been identified in Fufang E'jiao Jiang (FEJ), their hematopoietic effects and molecular mode of action are still not fully understood. In the current study, we analyzed the effects of martynoside, R-notoginsenoside R2 (R2), and 20S-ginsenoside Rg2 (Rg2) in a 5-fluorouracil-induced myelosuppression mouse model. Bone marrow nucleated cells (BMNCs) counts, hematopoietic progenitor cell colony-forming unit (CFU) assay, as well as flow cytometry analysis of Lin/c-kit/Sca-1 hematopoietic stem cell (HSC) population were conducted, and bone marrow cells were subjected to RNA sequencing. The transcriptome data were processed based on the differentially expressed genes. The results of the analysis show that each of the three compounds stimulates BMNCs and HSC growth, as well as burst-forming unit-erythroid and colony-forming unit granulocyte-monocyte colony expansion. The most relevant transcriptional changes appeared to be involved in regulation of hematopoietic cell lineage, NF-κB and TNF-α signaling, inhibition of inflammation, and acceleration of hematopoietic cell recovery. Notably, the individual compounds shared similar but specified transcriptome profiles. Taken together, the hematopoietic effects for the three tested compounds of FEJ are confirmed in this myelosuppression mouse model. The transcriptome maps of these effects provide valuable information concerning their underlying mechanisms and provide a framework for the continued study of the complex mode of action of FEJ.

摘要

尽管复方阿胶浆(FEJ)中已鉴定出多种生物活性成分,但其造血作用和分子作用模式仍未完全明确。在本研究中,我们在5-氟尿嘧啶诱导的骨髓抑制小鼠模型中分析了紫丁香苷、R-三七皂苷R2(R2)和20S-人参皂苷Rg2(Rg2)的作用。进行了骨髓有核细胞(BMNCs)计数、造血祖细胞集落形成单位(CFU)测定以及对Lin/c-kit/Sca-1造血干细胞(HSC)群体的流式细胞术分析,并对骨髓细胞进行了RNA测序。基于差异表达基因对转录组数据进行处理。分析结果表明,这三种化合物均能刺激BMNCs和HSC生长,以及红系爆式形成单位和粒-单核细胞集落形成单位集落扩增。最相关的转录变化似乎涉及造血细胞谱系调控、NF-κB和TNF-α信号传导、炎症抑制以及造血细胞恢复加速。值得注意的是,各化合物具有相似但特定的转录组图谱。综上所述,在该骨髓抑制小鼠模型中证实了FEJ的三种受试化合物的造血作用。这些作用的转录组图谱为其潜在机制提供了有价值的信息,并为继续研究FEJ复杂的作用模式提供了框架。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ebd9/6008481/dba7ee883e93/fphar-09-00616-g001.jpg

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