基于转录组数据多维度解析荷叶碱抗脑缺血的作用机制  

Multidimensional Analysis of Mechanisms of Nuciferine Against Cerebral Ischemia Based on Transcriptomic Data

作　　者：秦莹莹 李鹏[2] 陈莎[1] 刘艳[1] 程锦堂[1] 许青霞 王国华[1] 周静[1] 刘安[1] 陈畅[1,3] QIN Yingying;LI Peng;CHEN Sha;LIU Yan;CHENG Jintang;XU Qingxia;WANG Guohua;ZHOU Jing;LIU An;CHEN Chang(Institute of Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China;School of Basic Science,Shanxi Key Laboratory for Modernization of Traditional Chinese Veterinary Medicine,Shanxi Agricultural University,Jinzhong 030801,China;School of Chinese Materia Medica,Chongqing University of Chinese Medicine,Chongqing 402760,China)

机构地区：[1]中国中医科学院中药研究所,北京100700 [2]山西农业大学基础部,中兽医药现代化山西省重点实验室,山西晋中030801 [3]重庆中医药学院中药学院,重庆402760

出　　处：《中国实验方剂学杂志》2025年第9期184-191,共8页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：国家“重大新药创制”科技重大专项(2019ZX09201005);中国中医科学院科技创新工程项目(CI2021A00916,CI2021B004)。

摘　　要：目的:基于转录组数据,从组织、细胞、病理过程、生物过程和信号通路等多个维度,解析荷叶碱抗脑缺血的药理作用机制。方法:将30只SD大鼠按体质量随机分为假手术组、模型组和荷叶碱组(40 mg·kg^(-1)),除假手术组外,其余2组给药30 min后通过线栓法制备大鼠脑中动脉栓塞(MCAO)模型。术后24 h运用转录组测序技术检测大鼠脑组织皮层半暗带的基因表达谱,对差异表达基因进行基因本体(GO)与京都基因与基因组百科全书(KEGG)通路富集分析;采用基于转录组的多尺度网络药理学平台(TMNP)从组织、细胞、病理过程、生物过程及信号通路5个维度解析荷叶碱抗脑缺血的作用机制。结果:转录组测序及基因定量分析结果发现,共有667个荷叶碱明显逆转的基因,进一步通过KEGG和GO富集分析,发现荷叶碱的作用途径涉及调节应激反应、离子运输、细胞增殖与分化、突触功能等。TMNP研究发现,在组织水平上,荷叶碱可以明显改善缺血所导致的脑组织损伤;在细胞和病理水平上,荷叶碱可以通过改善多种神经细胞状态,调动免疫细胞、调节炎症反应等方面发挥抗脑缺血的作用;在生物过程和信号通路水平上,荷叶碱主要作用于血管重构、炎症相关信号通路及突触的信号传递等过程。结论:荷叶碱抗脑缺血的作用机制可能与干预应激反应和炎症过程、影响血管重构、调节突触功能等多个过程有关,可为深入研究荷叶碱抗脑缺血的药理机制提供依据和参考。Objective:Studies have shown that nuciferine has anti-cerebral ischemia effect,but the specific mechanism of action has not been elaborated.Based on the transcriptome results,the pharmacological mechanism of nuciferine against cerebral ischemia was analyzed from multiple dimensions including tissue,cell,pathological process,biological process and signaling pathway.Methods:Thirty SD rats were randomly divided into the sham group,model group and nuciferine group(40 mg·kg^(-1))according to weight.Except for the sham group,the model of middle cerebral artery occlusion(MCAO)was established by thread embolization method after 30 min of administration in the other two groups.Twenty-four hours after surgery,transcriptome sequencing was used to detect the gene expression profiles in the cortex penumbra of rat cerebral tissue,and gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis were performed for differentially expressed genes.The mechanismof nuciferine against cerebral ischemia was analyzed from 5 dimensions of tissue,cell,pathological process,biological process and signaling pathway by the transcriptome-based multi-scale network pharmacology platform(TMNP).Results:Transcriptome sequencing and gene quantitative analysis showed that 667 genes were significantly reversed by nuciferine.Further enrichment analysis of KEGG and GO suggested that the pathways of nuciferine involved regulating stress response,ion transport,cell proliferation and differentiation,and synaptic function.TMNP research found that at the tissue level,nuciferine could significantly improve the cerebral tissue injury caused by ischemia.At the cellular and pathological levels,nuciferine could play an anti-cerebral ischemia role by improving the state of various nerve cells,mobilizing immune cells,regulating inflammation.And at the level of biological processes and signaling pathways,nuciferine mainly acted on the processes such as vascular remodeling,inflammation-related signaling pathways,and synaptic signalin

关 键 词：荷叶碱 脑缺血 转录组 药理机制 炎症 应激反应 突触功能 血管重构 

分 类 号：R256[医药卫生—中医内科学] R743[医药卫生—中医学] Q344.13[生物学—遗传学]