小檗碱通过调控JAK/STAT通路减缓阿托伐他汀诱发的斑马鱼脑出血  

Berberine alleviates atorvastatin-induced intracerebral hemorrhage in zebrafish by regulating the JAK/STAT pathway

作　　者：刘馨妍 陈博[2] 蒋建东[1] 张靖溥[2] LIU Xin-yan;CHEN Bo;JIANG Jian-dong;ZHANG Jing-pu(Viral Laboratory,The Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China;Metabolic Engineering Laboratory,The Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences&Peking Union Medical College,Beijing 100050,China)

机构地区：[1]中国医学科学院北京协和医学院医药生物技术研究所病毒室,北京100050 [2]中国医学科学院北京协和医学院医药生物技术研究所微生物代谢工程室,北京100050

出　　处：《中国医药生物技术》2024年第4期298-307,共10页Chinese Medicinal Biotechnology

基　　金：中国医学科学院医学与健康科技创新工程(2021-I2M-1-030)。

摘　　要：目的探讨小檗碱(BBR)对阿托伐他汀(ATV)诱导的斑马鱼脑出血模型的保护作用及其潜在机制。方法利用ATV诱导斑马鱼脑出血模型,同时给予BBR,观察其出血情况及神经损伤,并对其出血后炎症因子和运动神经功能进行检测。分离斑马鱼脑部组织进行转录组测序分析,通过基因本体(GO)和基因与基因组百科全书(KEGG)数据库进行差异基因的功能分析,探寻BBR发挥作用的机制。结果2μmol/L的ATV可显著诱导斑马鱼幼鱼发生脑出血以及出血后损伤,80%斑马鱼在给药后48 h观察到严重出血,出血后神经元数量明显减少,斑马鱼运动距离缩短。在用BBR处理后平均出血面积由0.019 mm2下降至0.011 mm2,神经损伤及炎症情况有所缓解,运动距离比模型组明显增长。转录组测序发现,模型组和对照组的差异基因与BBR处理组和模型组的差异基因出现48个交集基因,对其进行KEGG分析,JAK/STAT信号通路显著富集,其中与脑出血相关的il11b、stat1b、lepa、lepb 4个基因发生显著变化,经qPCR验证与测序结果一致。结论BBR可以保护ATV诱导的斑马鱼脑出血及其出血后脑损伤,JAK/STAT信号途径可能是BBR发挥作用的潜在途径。Objective To investigate the protective effect of berberine(BBR)against atorvastatin(ATV)-induced zebrafish intracerebral hemorrhage(ICH)model.Methods An ATV zebrafish ICH model was used,with concurrent administration of BBR to observe hemorrhagic conditions,assess neural damage,analyze post-bleeding inflammatory factors,and evaluate swimming locomotion.Zebrafish brain tissue was isolated for transcriptome sequencing analysis,and differential gene function analysis was conducted using the gene ontology(GO)and kyoto encyclopedia of genes and genomes(KEGG)databases to explore the mechanism of BBR effects.Results ATV(2μmol/L)significantly induced cerebral hemorrhage and post-hemorrhagic injury in zebrafish juveniles,with severe hemorrhage observed in 80%of zebrafish at 48 hours post-administration.The number of neurons was significantly reduced after hemorrhage.Treatment with BBR resulted in a decrease in the average bleeding area from 0.019 mm2 to 0.011 mm2,along with alleviation of nerve damage and inflammation.Transcriptome sequencing revealed 48 overlapping genes among the differentially expressed genes(DEGs)in the model group vs.control group and the DEGs in the BBR treatment group vs.model group.KEGG analysis showed significant enrichment of the JAK/STAT signaling pathway.Four genes,il11b,stat1b,lepa and lepb,exhibited significant changes,which were validated through qPCR,confirming consistency with the sequencing results.Conclusion BBR protects against ATV cerebral hemorrhage and post-hemorrhagic brain damage in zebrafish,and the JAK/STAT signaling pathway may be involved in BBR effects.

关 键 词：斑马鱼 小檗碱 脑出血 JAK/STAT信号通路 

分 类 号：R285.5[医药卫生—中药学]